FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wahlster, S Williamson, C Shafi, M Westover, M AF Wahlster, Sarah Williamson, Craig Shafi, Mouhsin Westover, M. TI Sensitivity of Compressed Spectral Array Displays for Seizures and Other Critical Patterns in Adult Long Term EEG Monitoring SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Wahlster, Sarah; Williamson, Craig; Westover, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shafi, Mouhsin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01021 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600178 ER PT J AU Wahlster, S Berkowitz, A Zepeda, R Sagar, V Lyons, J Klein, J Mejia, N AF Wahlster, Sarah Berkowitz, Aaron Zepeda, Rodrigo Sagar, Vanya Lyons, Jennifer Klein, Joshua Mejia, Nicte TI Neurology and Global Health: Initiatives Led by Residents and Staff from the Partners Neurology Program SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Wahlster, Sarah; Berkowitz, Aaron; Sagar, Vanya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wahlster, Sarah; Berkowitz, Aaron; Sagar, Vanya; Lyons, Jennifer; Klein, Joshua] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zepeda, Rodrigo] Massachusetts Gen Hosp, Cambridge, MA USA. [Zepeda, Rodrigo] Brigham & Womens Hosp, Cambridge, MA USA. [Mejia, Nicte] Massachusetts Gen Hosp, Somerville, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN61010 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600081 ER PT J AU Wells, R Yeh, G Kerr, C Wolkin, J Davis, R Dossett, M Tan, Y Wall, R Walsh, J Kaptchuk, T Press, D Phillips, R Kong, J AF Wells, Rebecca Yeh, Gloria Kerr, Catherine Wolkin, Jennifer Davis, Roger Dossett, Michelle Tan, Ying Wall, Robert Walsh, Jacquelyn Kaptchuk, Ted Press, Daniel Phillips, Russell Kong, Jian TI Impact of Meditation on Default Mode Network & Hippocampus in Mild Cognitive Impairment: A Randomized Trial SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Wells, Rebecca] Wake Forest Baptist Hlth, Winston Salem, NC USA. [Yeh, Gloria; Davis, Roger; Dossett, Michelle; Kaptchuk, Ted; Phillips, Russell] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kerr, Catherine] Brown Univ, Sch Med, Pawtucket, RI USA. [Wolkin, Jennifer] NYU, Langone Med Ctr, New York, NY USA. [Tan, Ying] Massachusetts Gen Hosp, Charlestown, MA USA. [Wall, Robert] Commonwealth Care Alliance, Boston, MA USA. [Walsh, Jacquelyn] Brigham & Womens Hosp, Boston, MA 02115 USA. [Press, Daniel] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Winchester, MA USA. [Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01014 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600171 ER PT J AU Wigman, S Papp, K Bamfo, R Becker, A Johnson, K Sperling, R Rentz, D AF Wigman, Sarah Papp, Kathryn Bamfo, Rose Becker, Alex Johnson, Keith Sperling, Reisa Rentz, Dorene TI Are Problems Retrieving Proper Names a Harbinger of Disease in Older Adults? SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Wigman, Sarah] Brigham & Womens Hosp, Charlestown, MA USA. [Papp, Kathryn; Sperling, Reisa; Rentz, Dorene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bamfo, Rose] Massachusetts Gen Hosp, Charlestown, MA USA. [Becker, Alex; Johnson, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07146 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605128 ER PT J AU Wilson, M Bogoch, I Venna, N AF Wilson, Michael Bogoch, Isaac Venna, Nagagopal TI Subacute Segmental Lower Motor Neuron Syndrome Associated with Spinal Cord Gray Matter T2-Hyperintensities in 2 Patients with Well-Controlled HIV Infection SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Wilson, Michael] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bogoch, Isaac] Univ Toronto, Toronto, ON, Canada. [Venna, Nagagopal] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03250 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602218 ER PT J AU Baggett, TP Hwang, SW O'Connell, JJ Porneala, BC Stringfellow, EJ Orav, EJ Singer, DE Rigotti, NA AF Baggett, Travis P. Hwang, Stephen W. O'Connell, James J. Porneala, Bianca C. Stringfellow, Erin J. Orav, E. John Singer, Daniel E. Rigotti, Nancy A. TI Mortality Among Homeless Adults in Boston Shifts in Causes of Death Over a 15-Year Period SO JAMA INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; DEATH CERTIFICATES; COHORT; WOMEN; MEN; SHELTERS; HEALTH; RESIDENTS; ACCURACY; PROGRAMS AB Background: Homeless persons experience excess mortality, but US-based studies on this topic are outdated or lack information about causes of death. To our knowledge, no studies have examined shifts in causes of death for this population over time. Methods: We assessed all-cause and cause-specific mortality rates in a cohort of 28 033 adults 18 years or older who were seen at Boston Health Care for the Homeless Program from January 1, 2003, through December 31, 2008. Deaths were identified through probabilistic linkage to the Massachusetts death occurrence files. We compared mortality rates in this cohort with rates in the 2003-2008 Massachusetts population and a 1988-1993 cohort of homeless adults in Boston using standardized rate ratios with 95% confidence intervals. Results: A total of 1302 deaths occurred during 90 450 person-years of observation. Drug overdose (n=219), cancer (n=206), and heart disease (n=203) were the major causes of death. Drug overdose accounted for one-third of deaths among adults younger than 45 years. Opioids were implicated in 81% of overdose deaths. Mortality rates were higher among whites than nonwhites. Compared with Massachusetts adults, mortality disparities were most pronounced among younger individuals, with rates about 9-fold higher in 25- to 44-year-olds and 4.5-fold higher in 45- to 64-year-olds. In comparison with 1988-1993 rates, reductions in deaths from human immunodeficiency virus (HIV) were offset by 3- and 2-fold increases in deaths owing to drug overdose and psychoactive substance use disorders, resulting in no significant difference in overall mortality. Conclusions: The all-cause mortality rate among homeless adults in Boston remains high and unchanged since 1988 to 1993 despite a major interim expansion in clinical services. Drug overdose has replaced HIV as the emerging epidemic. Interventions to reduce mortality in this population should include behavioral health integration into primary medical care, public health initiatives to prevent and reverse drug overdose, and social policy measures to end homelessness. JAMA Intern Med. 2013;173(3):189-195. Published online January 14, 2013. doi:10.1001/jamainternmed.2013.1604 C1 [Baggett, Travis P.; O'Connell, James J.; Porneala, Bianca C.; Singer, Daniel E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Baggett, Travis P.; O'Connell, James J.; Orav, E. John; Singer, Daniel E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baggett, Travis P.; O'Connell, James J.; Stringfellow, Erin J.] Boston Hlth Care Homeless Program, Boston, MA USA. [Hwang, Stephen W.] Univ Toronto, St Michaels Hosp, Dept Med, Div Gen Internal Med, Toronto, ON M5B 1W8, Canada. [Stringfellow, Erin J.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Orav, E. John] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP Baggett, TP (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM tbaggett@partners.org RI Hwang, Stephen/D-2297-2011 OI Hwang, Stephen/0000-0002-1276-1101 FU General Medicine Division at Massachusetts General Hospital, Boston; BHCHP, Boston; National Institute on Drug Abuse of the National Institutes of Health [K23DA034008]; American Cancer Society [122269-IRG-12-070-01-IRG]; BHCHP FX Drs Baggett and O'Connell are staff physicians at BHCHP, where they receive financial compensation for rendering patient care services. At the time of the study, Ms Stringfellow was employed by BHCHP as a research coordinator.; Funding for this study was provided by the General Medicine Division at Massachusetts General Hospital and by BHCHP, both in Boston. Dr Baggett also receives funding from the National Institute on Drug Abuse of the National Institutes of Health under Award Number K23DA034008 and from the American Cancer Society under award No. 122269-IRG-12-070-01-IRG. NR 47 TC 70 Z9 70 U1 6 U2 40 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 11 PY 2013 VL 173 IS 3 BP 189 EP 195 DI 10.1001/jamainternmed.2013.1604 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 121JV UT WOS:000317240400010 PM 23318302 ER PT J AU Vijayaraghavan, M Penko, J Bangsberg, DR Miaskowski, C Kushel, MB AF Vijayaraghavan, Maya Penko, Joanne Bangsberg, David R. Miaskowski, Christine Kushel, Margot B. TI Opioid Analgesic Misuse in a Community-Based Cohort of HIV-Infected Indigent Adults SO JAMA INTERNAL MEDICINE LA English DT Letter ID CHRONIC NONCANCER PAIN; INDIVIDUALS C1 [Vijayaraghavan, Maya] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Penko, Joanne; Kushel, Margot B.] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. [Penko, Joanne; Kushel, Margot B.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Charlestown, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Kushel, MB (reprint author), Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, POB 1364, San Francisco, CA 94143 USA. EM margot.kushel@ucsf.edu FU NCRR NIH HHS [UL1RR024131]; NIDA NIH HHS [R01DA022550]; NIMH NIH HHS [R01MH54907] NR 9 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 11 PY 2013 VL 173 IS 3 BP 235 EP 237 DI 10.1001/jamainternmed.2013.1576 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 121JV UT WOS:000317240400021 PM 23319013 ER PT J AU Campbell, EG Pham-Kanter, G Vogeli, C Iezzoni, LI AF Campbell, Eric G. Pham-Kanter, Genevieve Vogeli, Christine Iezzoni, Lisa I. TI Physician Acquiescence to Patient Demands for Brand-Name Drugs: Results of a National Survey of Physicians SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Campbell, Eric G.; Vogeli, Christine; Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Campbell, Eric G.; Pham-Kanter, Genevieve; Vogeli, Christine; Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Pham-Kanter, Genevieve] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. [Pham-Kanter, Genevieve] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ecampbell@partners.org OI Pham-Kanter, Genevieve/0000-0002-3044-7829 NR 7 TC 12 Z9 12 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 11 PY 2013 VL 173 IS 3 BP 237 EP 239 DI 10.1001/jamainternmed.2013.1539 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121JV UT WOS:000317240400022 PM 23303297 ER PT J AU Demichelis, F Garraway, LA Rubin, MA AF Demichelis, Francesca Garraway, Levi A. Rubin, Mark A. TI Molecular Archeology: Unearthing Androgen-Induced Structural Rearrangements in Prostate Cancer Genomes SO CANCER CELL LA English DT Editorial Material ID TMPRSS2; FUSION AB In this issue of Cancer Cell, Weischenfeldt and colleagues report on the whole genome sequencing of 11 early-onset prostate cancers. Compared to elderly onset prostate cancer, these tumors demonstrate enrichment for androgen-driven structural rearrangements involving ETS family genes. This study confirms observations that prostate cancer manifests discrete genomic subclasses. C1 [Demichelis, Francesca] Univ Trent, Ctr Integrat Biol, I-38123 Povo, Trento, Italy. [Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Demichelis, Francesca] Cornell Univ, Weill Cornell Med Coll, Inst Computat Biomed, Dept Physiol & Biophys, New York, NY 10065 USA. [Rubin, Mark A.] Cornell Univ, Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Rubin, Mark A.] Cornell Univ, Weill Cornell Med Coll, Brady Fdn, Dept Urol, New York, NY 10065 USA. [Rubin, Mark A.] Cornell Univ, Weill Cornell Med Coll, Inst Precis Med, New York, NY 10065 USA. [Rubin, Mark A.] New York Presbyterian Hosp, New York, NY 10065 USA. RP Rubin, MA (reprint author), Cornell Univ, Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. EM rubinma@med.cornell.edu OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [R01 CA125612, U01 CA111275, U01CA111275] NR 10 TC 1 Z9 1 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB 11 PY 2013 VL 23 IS 2 BP 133 EP 135 DI 10.1016/j.ccr.2013.01.019 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 091RO UT WOS:000315067700002 PM 23410968 ER PT J AU Davids, MS Letai, A AF Davids, Matthew S. Letai, Anthony TI ABT-199: Taking Dead Aim at BCL-2 SO CANCER CELL LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; FAMILY; ABT-737 AB ABT-199 is a new selective small molecule inhibitor of BCL-2 that appears to spare platelets while achieving potent antitumor activity. Assays that can predict the efficacy of ABT-199 in individual tumors will be critical in determining how best to incorporate this promising agent into the armamentarium of cancer therapies. C1 [Davids, Matthew S.; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu RI Jones, Jeffrey/E-9827-2013 FU NCI NIH HHS [R01 CA129974, T32 CA009172] NR 10 TC 35 Z9 35 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB 11 PY 2013 VL 23 IS 2 BP 139 EP 141 DI 10.1016/j.ccr.2013.01.018 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 091RO UT WOS:000315067700005 PM 23410971 ER PT J AU Malin, JL Weeks, JC Potosky, AL Hornbrook, MC Keating, NL AF Malin, Jennifer L. Weeks, Jane C. Potosky, Arnold L. Hornbrook, Mark C. Keating, Nancy L. TI Medical Oncologists' Perceptions of Financial Incentives in Cancer Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COST SAVINGS; CHEMOTHERAPY; TRENDS; LIFE; END; AGGRESSIVENESS; PATTERNS; SERVICES; OUTCOMES; PROGRAM AB Purpose The cost of cancer care continues to increase at an unprecedented rate. Concerns have been raised about financial incentives associated with the chemotherapy concession in oncology practices and their impact on treatment recommendations. Methods The objective of this study was to measure the physician-reported effects of prescribing chemotherapy or growth factors or making referrals to other cancer specialists, hospice, or hospital admissions on medical oncologists' income. US medical oncologists involved in the care of a population-based cohort of patients with lung or colorectal cancer from the Cancer Care Outcomes Research and Surveillance (CanCORS) study were surveyed regarding their perceptions of the impact of prescribing practices or referrals on their income. Results Although most oncologists reported that their incomes would be unaffected, compared with salaried oncologists, physicians in fee-for-service practice, and those paid a salary with productivity incentives were more likely to report that their income would increase from administering chemotherapy (odds ratios [ORs], 7.05 and 7.52, respectively; both P < .001) or administering growth factors (ORs, 5.60 and 6.03, respectively; both P < .001). Conclusion A substantial proportion of oncologists who are not paid a fixed salary report that their incomes increase when they administer chemotherapy and growth factors. Further research is needed to understand the impact of these financial incentives on both the quality and cost of care. J Clin Oncol 31:530-535. (C) 2012 by American Society of Clinical Oncology C1 [Malin, Jennifer L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Malin, Jennifer L.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. RP Malin, JL (reprint author), WellPoint, 1 WellPoint Way, Thousand Oaks, CA 91362 USA. EM jennifer.malin@wellpoint.com FU National Cancer Institute (NCI) [U01 CA093344]; Dana-Farber Cancer Institute/Cancer Research Network [U01 CA093332]; Harvard Medical School/Northern California Cancer Center [U01 CA093324]; RAND/University of California, Los Angeles [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA01013]; University of North Carolina [U01 CA093326]; Department of Veterans Affairs (VA) [CRS 02-164] FX Supported by Grants No. U01 CA093344 from the National Cancer Institute (NCI) to the Statistical Coordinating Center, U01 CA093332 from the Dana-Farber Cancer Institute/Cancer Research Network, U01 CA093324 from Harvard Medical School/Northern California Cancer Center, U01 CA093348 from RAND/University of California, Los Angeles, U01 CA093329 from the University of Alabama at Birmingham, U01 CA01013 from the University of Iowa, U01 CA093326 from the University of North Carolina, and CRS 02-164 from the Department of Veterans Affairs (VA) to the Durham VA Medical Center. NR 27 TC 17 Z9 17 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2013 VL 31 IS 5 BP 530 EP 535 DI 10.1200/JCO.2012.43.6063 PG 6 WC Oncology SC Oncology GA 088FY UT WOS:000314820400009 PM 23269996 ER PT J AU Chen, AB Cronin, A Weeks, JC Chrischilles, EA Malin, J Hayman, JA Schrag, D AF Chen, Aileen B. Cronin, Angel Weeks, Jane C. Chrischilles, Elizabeth A. Malin, Jennifer Hayman, James A. Schrag, Deborah TI Palliative Radiation Therapy Practice in Patients With Metastatic Non-Small-Cell Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-of-Radiation-Oncology (ASTRO) CY OCT 01-06, 2011 CL Miami Beach, FL SP Amer Soc Radiat Oncol (ASTRO) ID PAINFUL BONE METASTASES; SINGLE-FRACTION; THORACIC RADIOTHERAPY; MULTIPLE IMPUTATION; SURVIVAL; TRIALS; GY; PREFERENCES; SCHEDULE; ONCOLOGY AB Purpose Randomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods From patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression. Results Of 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest. Conclusion When palliative RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery. J Clin Oncol 31:558-564. (C) 2013 by American Society of Clinical Oncology C1 [Chen, Aileen B.; Cronin, Angel; Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02215 USA. [Chen, Aileen B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chrischilles, Elizabeth A.] Univ Iowa, Iowa City, IA USA. [Malin, Jennifer] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Hayman, James A.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1111, Boston, MA 02215 USA. EM achen7@partners.org OI Chen, Aileen/0000-0002-5385-3360 FU NCI NIH HHS [U01 CA093324, U01 CA093326, U01 CA093348, U01 CA093332, K05 CA166208, U01 CA093339, U01 CA093329, P30 CA086862, U01 CA093344] NR 42 TC 30 Z9 31 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2013 VL 31 IS 5 BP 558 EP 564 DI 10.1200/JCO.2012.43.7954 PG 7 WC Oncology SC Oncology GA 088FY UT WOS:000314820400013 PM 23295799 ER PT J AU Unguru, Y Joffe, S Fernandez, CV Yu, AL AF Unguru, Yoram Joffe, Steven Fernandez, Conrad V. Yu, Alice L. TI Ethical Issues for Control-Arm Patients After Revelation of Benefits of Experimental Therapy: A Framework Modeled in Neuroblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CHILDRENS ONCOLOGY GROUP; PHASE-I; CLINICAL-RESEARCH; POSTTRIAL ACCESS; UNITED-STATES; ANTIBODY; CH14.18; TRIAL; DRUGS AB In 2009, the Children's Oncology Group (COG) phase III randomized controlled trial, ANBL0032, found that adding immunotherapy (Ch14.18) to standard therapy significantly improved outcomes in patients with high-risk neuroblastoma when administered within 110 days after autologous stem-cell transplantation (SCT). After careful deliberation and consultation, the COG Neuroblastoma Committee decided to offer Ch14.18 to prior trial participants who had been randomly assigned to the control arm (no immunotherapy), regardless of the time that had elapsed since SCT. This decision occurred in the context of a limited supply of Ch14.18 and no data regarding its role when administered beyond 110 days. In this article, we analyze the numerous ethical challenges highlighted by the ANBL0032 trial, including the limits of researchers' reciprocity-based obligations to study participants, post-trial access to beneficial therapies, and the balance between scientific knowledge and parental hope. These deliberations may be useful to other researchers when considering their ethical obligations to control-arm participants in the wake of a positive randomized trial. J Clin Oncol 31:641-646. (C) 2013 by American Society of Clinical Oncology C1 [Unguru, Yoram] Herman & Walter Samuelson Childrens Hosp Sinai, Baltimore, MD 21215 USA. [Unguru, Yoram] Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Boston Childrens Hosp, Boston, MA USA. [Fernandez, Conrad V.] Dalhousie Univ, Halifax, NS, Canada. [Yu, Alice L.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Unguru, Y (reprint author), Herman & Walter Samuelson Childrens Hosp Sinai, Div Pediat Hematol Oncol, 2401 W Belvedere Ave, Baltimore, MD 21215 USA. EM yunguru@lifebridgehealth.org OI Joffe, Steven/0000-0002-0667-7384 FU National Cancer Institute [UA CA098543-06] FX Supported by Grant No. UA CA098543-06 from the National Cancer Institute to the Children's Oncology Group. NR 31 TC 5 Z9 5 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2013 VL 31 IS 5 BP 641 EP 646 DI 10.1200/JCO.2012.47.1227 PG 6 WC Oncology SC Oncology GA 088FY UT WOS:000314820400023 PM 23295797 ER PT J AU Corrales-Medina, VF Musher, DM Shachkina, S Chirinos, JA AF Corrales-Medina, Vicente F. Musher, Daniel M. Shachkina, Svetlana Chirinos, Julio A. TI Acute pneumonia and the cardiovascular system SO LANCET LA English DT Review ID COMMUNITY-ACQUIRED PNEUMONIA; ANGIOTENSIN-CONVERTING ENZYME; ACUTE CORONARY SYNDROMES; THROMBOSIS-INDUCING ACTIVITY; SHORT-TERM MORTALITY; ACUTE KIDNEY INJURY; RISK-FACTORS; BACTERIAL PNEUMONIA; NATRIURETIC PEPTIDE; PNEUMOCOCCAL PNEUMONIA AB Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research. C1 [Corrales-Medina, Vicente F.; Shachkina, Svetlana] Univ Ottawa, Dept Med, Ottawa, ON K1Y 4E9, Canada. [Corrales-Medina, Vicente F.; Shachkina, Svetlana] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Musher, Daniel M.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Houston, TX USA. [Chirinos, Julio A.] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Corrales-Medina, VF (reprint author), Univ Ottawa, Dept Med, 1053 Carling Ave,CPC 470, Ottawa, ON K1Y 4E9, Canada. EM vcorrales@toh.on.ca OI Corrales-Medina, Vicente/0000-0002-9691-491X FU Research Priority Grant from the Department of Medicine of The Ottawa Hospital; Junior Investigator Award of the Ottawa Hospital Research Institute FX We thank Alexandra Davis, librarian at The Ottawa Hospital, for her assistance in the design of our search strategies and the retrieval of selected articles. We also acknowledge Yoko S Schreiber and Bing Wang, from the Division of Infectious Diseases at the University of Ottawa, for their assistance with the translation of articles in French, German, and Chinese; and Waheed Raja and Zubair A Khan, from the Divisions of Internal Medicine at Texas Tech University Health Sciences Center and Cooper University Hospital, respectively, for their helpful assistance during the literature search process. VFC-M is supported by a Research Priority Grant from the Department of Medicine of The Ottawa Hospital, and a Junior Investigator Award of the Ottawa Hospital Research Institute. NR 100 TC 58 Z9 60 U1 2 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB 9 PY 2013 VL 381 IS 9865 BP 496 EP 505 DI 10.1016/S0140-6736(12)61266-5 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 088CH UT WOS:000314810900035 PM 23332146 ER PT J AU Koch, MR Jagannathan, JP Shinagare, AB Krajewski, KM Raut, CP Hornick, JL Ramaiya, NH AF Koch, M. R. Jagannathan, J. P. Shinagare, A. B. Krajewski, K. M. Raut, C. P. Hornick, J. L. Ramaiya, N. H. TI Imaging features of primary anorectal gastrointestinal stromal tumors with clinical and pathologic correlation SO CANCER IMAGING LA English DT Article DE Gastrointestinal stromal tumor; anorectal; CT; MRI; FDG-PET/CT ID TERM-FOLLOW-UP; INTERSTITIAL-CELLS; IMATINIB MESYLATE; RECTUM; PROGNOSIS; BIOLOGY; COLON; CAJAL AB Purpose: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. Materials and methods: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30-89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). Results: The mean tumor size was 6.9 x 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso-to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4-16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. Conclusion: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without lymphadenopathy or intestinal obstruction. C1 [Koch, M. R.; Jagannathan, J. P.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Jagannathan, J. P.; Shinagare, A. B.; Krajewski, K. M.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Raut, C. P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Hornick, J. L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org NR 21 TC 4 Z9 4 U1 0 U2 1 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD FEB 8 PY 2013 VL 12 IS 3 BP 557 EP 565 DI 10.1102/1470-7330.2012.0048 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172MZ UT WOS:000321009500004 PM 23400107 ER PT J AU Liu, N Yu, ZY Li, YD Yuan, J Zhang, J Xiang, SL Wang, XY AF Liu, Ning Yu, Zhanyang Li, Yadan Yuan, Jing Zhang, Jian Xiang, Shuanglin Wang, Xiaoying TI Transcriptional regulation of mouse neuroglobin gene by cyclic AMP responsive element binding protein (CREB) in N2a cells SO NEUROSCIENCE LETTERS LA English DT Article DE Neuroglobin; CREB; Transcriptional regulation; Mouse; N2a cells ID NEURONAL CELLS; EXPRESSION; PROMOTER; HYPOXIA; INDUCTION; INJURY; REGION; BRAIN AB Neuroglobin (Ngb) has been demonstrated to be a novel neuroprotective protein that protects against hypoxia/ischemia and oxidative stress-induced injury in the nervous system. However, the regulation mechanisms of Ngb gene expression under both normal resting and stress conditions have not been fully elucidated. The cyclic AMP response element binding protein (CREB) is a key transcription factor that regulates a variety of pro-survival genes, but its role in regulating the neuroprotective gene Ngb has not been studied. In this study we investigated the transcriptional regulation of mouse Ngb gene by CREB in mouse neuroblastoma cell line N2a. Our results showed that CREB knockdown decreased Ngb gene expression, and overexpression of the wild-type CREB, but not the mutant CREB, significantly increased Ngb gene expression in N2a cells. Moreover, a CAMP response element (CRE) site located at -854 in the promoter region of mouse Ngb gene was found to be responsible for both basal and CREB-induced Ngb promoter activity. Using chromatin immunopreciptation (ChIP) assays, we found that CREB could bind to the Ngb promoter region spanning from -1016 to -793 that harbors the CRE site. Taken together, our results suggested that transcription factor CREB participates in the transcriptional regulation of mouse Ngb gene. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Liu, Ning; Yu, Zhanyang; Li, Yadan; Wang, Xiaoying] Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Liu, Ning; Yu, Zhanyang; Li, Yadan; Wang, Xiaoying] Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Liu, Ning; Yuan, Jing; Zhang, Jian; Xiang, Shuanglin] Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Coll Life Sci, Changsha 410081, Hunan, Peoples R China. RP Wang, XY (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol,Massachusetts Gen Hosp, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM xshlin@hunnu.edu.cn; wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476]; American Heart Association [12POST9720007] FX This work was supported in part by NIH grant R01-NS049476 (to X.W.) and postdoctoral fellowship (12POST9720007) from American Heart Association (to Z.Y.). We appreciate Dr. Eng H. Lo for his very helpful discussion. The authors declare no conflict of interest. NR 23 TC 13 Z9 14 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 8 PY 2013 VL 534 BP 333 EP 337 DI 10.1016/j.neulet.2012.11.025 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 160AL UT WOS:000320088300062 PM 23182882 ER PT J AU Kashiwagi, S Atochin, DN Li, Q Schleicher, M Pong, T Sessa, WC Huang, PL AF Kashiwagi, Satoshi Atochin, Dmitriy N. Li, Qian Schleicher, Michael Pong, Terrence Sessa, William C. Huang, Paul L. TI eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Nitric oxide; Endothelium; Insulin resistance; Diabetes; Metabolism; Obesity ID NITRIC-OXIDE SYNTHASE; VASCULAR ENDOTHELIAL-CELLS; ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; GLUCOSE-UPTAKE; MICE LACKING; MITOCHONDRIAL BIOGENESIS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; DIABETES-MELLITUS AB Phosphoxylation of endothelial nitric oxide synthase (eNOS) is an important regulator of its enzymatic activity. We generated knockin mice expressing phosphomimetic (SD) and unphosphorylatable (SA) eNOS mutations at S1176 to study the role of eNOS phosphorylation. The single amino acid SA mutation is associated with hypertension and decreased vascular reactivity, while the SD mutation results in increased basal and stimulated endothelial NO production. In addition to these vascular effects, modulation of the S1176 phosphorylation site resulted in unanticipated effects on metabolism. The eNOS SA mutation results in insulin resistance, hyperinsulinemia, adiposity, and increased weight gain on high fat. In contrast, the eNOS SD mutation is associated with decreased insulin levels and resistance to high fat-induced weight gain. These results demonstrate the importance of eNOS in regulation of insulin sensitivity, energy metabolism, and bodyweight regulation, and suggest eNOS phosphorylation as a novel target for the treatment of obesity and insulin resistance. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kashiwagi, Satoshi; Atochin, Dmitriy N.; Li, Qian; Pong, Terrence; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kashiwagi, Satoshi; Atochin, Dmitriy N.; Li, Qian; Pong, Terrence; Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Schleicher, Michael; Sessa, William C.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06536 USA. [Schleicher, Michael; Sessa, William C.] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06536 USA. RP Huang, PL (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp,Cardiol Div, 149 13th St, Charlestown, MA 02129 USA. EM phuang1@partners.org RI Atochin, Dmitriy/Q-3150-2016 FU NHLBI NIH HHS [R01 HL057818]; NINDS NIH HHS [R01 NS033335, R01 NS048426] NR 47 TC 12 Z9 13 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 8 PY 2013 VL 431 IS 2 BP 284 EP 290 DI 10.1016/j.bbrc.2012.12.110 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 095HM UT WOS:000315325300030 PM 23291238 ER PT J AU Martin, LS Castano, A Bravo, M Tavares, M Niederman, R Ogunbodede, EO AF San Martin, Laura Castano, Antonio Bravo, Manuel Tavares, Mary Niederman, Richard Ogunbodede, Eyitope O. TI Dental sealant knowledge, opinion, values and practice of Spanish dentists SO BMC ORAL HEALTH LA English DT Article DE Fissure sealants; Dental; Prevention; Children; Oral health ID FLUORIDE VARNISH; FISSURE SEALANTS; ORAL-HEALTH; CARIES; RECOMMENDATIONS; CHILDREN; ADOLESCENTS; STRATEGIES; BEHAVIOR; TRIAL AB Background: Multiple guidelines and systematic reviews recommend sealant use to reduce caries risk. Yet, multiple reports also indicate that sealants are significantly underutilized. This study examined the knowledge, opinions, values, and practice (KOVP) of dentists concerning sealant use in the southwest region of Andalusia, Spain. This is a prelude to the generation of a regional plan for improving children's oral health in Andalusia. Methods: The survey's target population was dentists working in western Andalusia, equally distributed in the provinces of Seville, Cadiz, and Huelva (N=2,047). A convenience sample of meeting participants and meeting participant email lists (N=400) were solicited from the annual course on Community and Pediatric Dentistry. This course is required for all public health sector dentists, and is open to all private sector dentists. Information on the dentist's KOVP of sealants was collected using four-part questionnaire with 31, 5-point Likert-scaled questions. Results: The survey population demographics included 190 men (48%) and 206 women (52%) with an average clinical experience of 10.6 (+/- 8.4) years and 9.3 (+/- 7.5) years, respectively. A significant sex difference was observed in the distribution of place of work (urban/suburb) (p=0.001), but no sex differences between working sector (public/private). The mean +/- SD values for each of the four KOVP sections for pit and fissure sealants were: knowledge = 3.57 +/- 0.47; opinion = 2.48 +/- 0.47; value = 2.74 +/- 0.52; and practice = 3.48 +/- 0.50. No sex differences were found in KOVP (all p > 0.4). Independent of sex: knowledge statistically differed by years of experience and place of work; opinion statistically differed by years of experience and sector; and practice statistically differed by years of experience and sector. Less experienced dentists tended to have slightly higher scores (similar to 0.25 on a Likert 1-5 scale). Statistically significant correlations were found between knowledge and practice (r=0.44, p=0.00) and between opinion and value (r=0.35, p=0.00). Conclusions: The results suggest that, similar to other countries, Andalusian dentists know that sealants are effective, have neutral to positive attitudes toward sealants; though, based on epidemiological studies, underuse sealants. Therefore, methods other than classical behavior change (eg: financial or legal mechanisms) will be required to change practice patterns aimed at improving children's oral health. C1 [San Martin, Laura; Castano, Antonio] Univ Seville, Sch Dent, Seville, Spain. [San Martin, Laura; Tavares, Mary; Niederman, Richard] Forsyth Inst, Cambridge, MA USA. [San Martin, Laura] Harvard Univ, Sch Dent Med Boston, Boston, MA 02115 USA. [Bravo, Manuel] Univ Granada, Sch Dent, Granada, Spain. [Tavares, Mary] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Ogunbodede, Eyitope O.] Obafemi Awolowo Univ, Fac Dent, Ife, Nigeria. RP Martin, LS (reprint author), Univ Seville, Sch Dent, Avicena S-N, Seville, Spain. EM LSanMartin@us.es OI niederman, richard/0000-0001-6674-1774 FU NIMHD [1 R34 DE022272 (NIH2385)]; NIDCR [1 U24 MD006964] FX The authors would like to thank the Vicerrectorado de Investigacion of the University of Seville, Harvard School of Dental Medicine, and the Forsyth Institute. We would also like to thank the following clinicians who participated in the validation of the survey: Drs. Anibal Gonzalez, Rafael Llamas, Maria del Aguila Cordero, David Ribas, Emilio Lledo, Manuel Poyato, Antonio Fernandez. We acknowledge the following sources for invaluable financial support NIMHD 1 R34 DE022272 (NIH2385) and NIDCR 1 U24 MD006964. We are grateful to Dr. Javier Gil for assistance with the statistical analysis. NR 40 TC 1 Z9 1 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6831 J9 BMC ORAL HEALTH JI BMC Oral Health PD FEB 8 PY 2013 VL 13 AR 12 DI 10.1186/1472-6831-13-12 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 099BK UT WOS:000315593700001 ER PT J AU Paintlia, MK Paintlia, AS Singh, AK Singh, I AF Paintlia, Manjeet K. Paintlia, Ajaib S. Singh, Avtar K. Singh, Inderjit TI S-Nitrosoglutathione Induces Ciliary Neurotrophic Factor Expression in Astrocytes, Which Has Implications to Protect the Central Nervous System under Pathological Conditions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; ACTIVATED-RECEPTOR-GAMMA; TRAUMATIC BRAIN-INJURY; NITRIC-OXIDE ACTIVATION; IN-VITRO; SIGNALING PATHWAY; GLIAL-CELLS; CYCLOOXYGENASE-2 EXPRESSION; OLIGODENDROCYTE PROGENITORS; DEMYELINATING DISEASES AB Accumulating evidence suggests that reactive astrogliosis has beneficial and detrimental outcomes in various CNS disorders, but the mechanism behind this dichotomy is unclear. Recent advances in this direction suggested that NO signaling is critical to regulate the outcomes of reactive astrogliosis in vivo. Using biochemical and genetic approaches, we here investigated the effect of S-nitrosoglutathione (GSNO; a physiological NO donor) in astrocytes in vitro settings. GSNO enhanced the expressions of glial fibrillary acidic protein and neurotrophic factors including ciliary neurotrophic factor (CNTF) in astrocytes in a dose-dependent manner. The enhanced CNTF expression in GSNO-treated astrocytes was ascribed to NO-mediated sGC/cGMP/PKG signaling. It was associated with p38 MAPK-dependent increased peroxisome proliferator-activated receptor-gamma transactivation. In addition, the chromatin accessibility of peroxisome proliferator-activated receptor-gamma accompanied with ATF2 and CREB (cAMP-response element-binding protein) was enhanced across the CNTF gene promoter in GSNO treated astrocytes. Interestingly, secreted CNTF was responsible for increased expression of glial fibrillary acidic protein in GSNO-treated astrocytes in an autocrine manner via a JAK2- and STAT3-dependent mechanism. In addition, CNTF secreted by GSNO-treated astrocytes enhanced the differentiation of immature oligodendrocytes in vitro. These effects of GSNO were consistent with an endogenously produced NO in astrocytes stimulated with proinflammatory cytokines in vitro. We conclude that NO signaling induces CNTF expression in astrocytes that favors the beneficial outcomes of reactive astrogliosis in vivo. Our data suggest that the endogenously produced NO or its exogenous source has potential to modulate the outcomes of reactive astrogliosis to protect CNS under pathological conditions. C1 [Paintlia, Manjeet K.; Paintlia, Ajaib S.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU National Institutes of Health [NS-22576, NS-37766, VA-1BX001072, VA-BX001999, C06 RR018823, C06 RR015455] FX This work was supported, in whole or in part, by National Institutes of Health Grants NS-22576, NS-37766, VA-1BX001072, VA-BX001999, C06 RR018823, and C06 RR015455. NR 69 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 8 PY 2013 VL 288 IS 6 BP 3831 EP 3843 DI 10.1074/jbc.M112.405654 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088OP UT WOS:000314845000015 PM 23264628 ER PT J AU Foerch, C Rosidi, NL Schlunk, F Lauer, A Cianchetti, FA Mandeville, E Arai, K Yigitkanli, K Fan, X Wang, X van Leyen, K Steinmetz, H Schaffer, CB Lo, EH AF Foerch, Christian Rosidi, Nathanael L. Schlunk, Frieder Lauer, Arne Cianchetti, Flor A. Mandeville, Emiri Arai, Ken Yigitkanli, Kazim Fan, Xiang Wang, Xiaoying van Leyen, Klaus Steinmetz, Helmuth Schaffer, Chris B. Lo, Eng H. TI Intravenous tPA Therapy Does Not Worsen Acute Intracerebral Hemorrhage in Mice SO PLOS ONE LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; SUBARACHNOID HEMORRHAGE; RAT MODEL; STROKE; THROMBOLYSIS; INHIBITION; PROTEIN; INJURY AB Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy. C1 [Foerch, Christian; Schlunk, Frieder; Lauer, Arne; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA 02114 USA. [Foerch, Christian; Schlunk, Frieder; Lauer, Arne; Steinmetz, Helmuth] Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany. [Rosidi, Nathanael L.; Cianchetti, Flor A.; Schaffer, Chris B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. RP Foerch, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA 02114 USA. EM foerch@em.uni-frankfurt.de RI van Leyen, Klaus/C-9126-2013; Schaffer, Chris/A-7409-2008 OI Schaffer, Chris/0000-0002-7800-9596 FU National Institutes of Health [R37-NS37074, R01-NS56458, P01-NS55104] FX This work was supported in part by National Institutes of Health grants R37-NS37074, R01-NS56458 and P01-NS55104. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 8 Z9 8 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 8 PY 2013 VL 8 IS 2 AR e54203 DI 10.1371/journal.pone.0054203 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086CJ UT WOS:000314660300005 PM 23408937 ER PT J AU Ding, QR Lee, YK Schaefer, EAK Peters, DT Veres, A Kim, K Kuperwasser, N Motola, DL Meissner, TB Hendriks, WT Trevisan, M Gupta, RM Moisan, A Banks, E Friesen, M Schinzel, RT Xia, F Tang, A Xia, YL Figueroa, E Wann, A Ahfeldt, T Daheron, L Zhang, F Rubin, LL Peng, LF Chung, RT Musunuru, K Cowan, CA AF Ding, Qiurong Lee, Youn-Kyoung Schaefer, Esperance A. K. Peters, Derek T. Veres, Adrian Kim, Kevin Kuperwasser, Nicolas Motola, Daniel L. Meissner, Torsten B. Hendriks, William T. Trevisan, Marta Gupta, Rajat M. Moisan, Annie Banks, Eric Friesen, Max Schinzel, Robert T. Xia, Fang Tang, Alexander Xia, Yulei Figueroa, Emmanuel Wann, Amy Ahfeldt, Tim Daheron, Laurence Zhang, Feng Rubin, Lee L. Peng, Lee F. Chung, Raymond T. Musunuru, Kiran Cowan, Chad A. TI A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models SO CELL STEM CELL LA English DT Article ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; MICE LACKING; DNA; EFFECTORS; PERILIPIN; NUCLEASES; SORTILIN; MUTATION; AKT2 AB Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease-dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor-neuron death, and hepatitis C infection. We found little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease. C1 [Ding, Qiurong; Lee, Youn-Kyoung; Peters, Derek T.; Veres, Adrian; Kim, Kevin; Kuperwasser, Nicolas; Meissner, Torsten B.; Hendriks, William T.; Trevisan, Marta; Gupta, Rajat M.; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Daheron, Laurence; Rubin, Lee L.; Musunuru, Kiran; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hendriks, William T.; Trevisan, Marta; Daheron, Laurence; Rubin, Lee L.; Musunuru, Kiran; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Schaefer, Esperance A. K.; Motola, Daniel L.; Rubin, Lee L.; Peng, Lee F.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Schaefer, Esperance A. K.; Peters, Derek T.; Veres, Adrian; Motola, Daniel L.; Gupta, Rajat M.; Peng, Lee F.; Chung, Raymond T.; Musunuru, Kiran; Cowan, Chad A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kuperwasser, Nicolas; Gupta, Rajat M.; Musunuru, Kiran] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Moisan, Annie] Roche Pharmaceut, Metab Discovery & Translat Area, CH-4070 Basel, Switzerland. [Banks, Eric; Zhang, Feng; Musunuru, Kiran; Cowan, Chad A.] Broad Inst, Cambridge, MA 02142 USA. [Zhang, Feng] MIT, McGovern Inst Brain Res, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Musunuru, K (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM kiranmusunuru@gmail.com; ccowan@fas.harvard.edu RI Ahfeldt, Tim/E-2935-2017; OI Kim, Kevin/0000-0002-7015-5871 FU Roche Postdoctoral Fellowship; Harvard Stem Cell Institute; Harvard Presidential Scholars Fund of the Harvard Medical School MD/PhD Program; United States National Institutes of Health [T32-DK007191, T32-HL007604, K08-DK088951, K24-DK078772, P01-NS066888, R00-HL098364, U01-HL107440, R01-DK097768]; New York Stem Cell Foundation; Broad Institute's Lawrence H. Summers Fellowship; Carlos Slim Foundation; Harvard University FX This work was supported in part by a Roche Postdoctoral Fellowship (Q. D.); the Sternlicht Director's Fund Award for Graduate Students from the Harvard Stem Cell Institute (D. T. P.); the Harvard Presidential Scholars Fund of the Harvard Medical School MD/PhD Program (A. V.); grants T32-DK007191 (E. A. K. S. and D. L. M.), T32-HL007604 (R. M. G.), K08-DK088951 (L. F. P.), K24-DK078772 (R. T. C.), P01-NS066888 (L. L. R.), R00-HL098364 (K. M.), U01-HL107440 (C. A. C.), and R01-DK097768 (F.Z., K. M., and C. A. C.) from the United States National Institutes of Health; the New York Stem Cell Foundation (L. L. R.); the Broad Institute's Lawrence H. Summers Fellowship and the Carlos Slim Foundation (K. M.); the Harvard Stem Cell Institute (T. B. M., L. L. R., K. M., and C. A. C.); and Harvard University (L. L. R., K. M., and C. A. C.). A. M. is a full-time employee of Roche Pharmaceuticals. We thank David Altshuler, Noel Burtt, Guillermo del Angel, Mark DePristo, Stacey Gabriel, Namrata Gupta, J. Keith Joung, Adam Kaplan, Ami Levy-Moonshine, Heng Li, Elyse Macksoud, Khalid Shakir, Alanna Strong, Kristin Thompson, Jayaraj Rajagopal, Stephanie Regan, Jennifer Shay, and the staffs of the HSCRB-HSCI Flow Cytometry Core and the Broad Institute's Genomics Platform for assistance and suggestions. NR 46 TC 227 Z9 250 U1 13 U2 92 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD FEB 7 PY 2013 VL 12 IS 2 BP 238 EP 251 DI 10.1016/j.stem.2012.11.011 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VB UT WOS:000329569300014 PM 23246482 ER PT J AU Wang, S Bates, J Li, XJ Schanz, S Chandler-Militello, D Levine, C Maherali, N Studer, L Hochedlinger, K Windrem, M Goldman, SA AF Wang, Su Bates, Janna Li, Xiaojie Schanz, Steven Chandler-Militello, Devin Levine, Corri Maherali, Nimet Studer, Lorenz Hochedlinger, Konrad Windrem, Martha Goldman, Steven A. TI Human iPSC-Derived Oligodendrocyte Progenitor Cells Can Myelinate and Rescue a Mouse Model of Congenital Hypomyelination SO CELL STEM CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; TRANSCRIPTION FACTOR; HUMAN ES; DIFFERENTIATION; DISEASE; LINEAGE; BRAIN; FETAL; IDENTIFICATION; REMYELINATE AB Neonatal engraftment by oligodendrocyte progenitor cells (OPCs) permits the myelination of the congenitally dysmyelinated brain. To establish a potential autologous source of these cells, we developed a strategy by which to differentiate human induced pluripotent stem cells (hiPSCs) into OPCs. From three hiPSC lines, as well as from human embryonic stem cells (hESCs), we generated highly enriched OLIG2(+)/PDGFR alpha(+)/NKX2.2(+)/SOX10(+) human OPCs, which could be further purified using fluorescence-activated cell sorting. hiPSC OPCs efficiently differentiated into both myelinogenic oligodendrocytes and astrocytes, in vitro and in vivo. Neonatally engrafted hiPSC OPCs robustly myelinated the brains of myelin-deficient shiverer mice and substantially increased their survival. The speed and efficiency of myelination by hiPSC OPCs was higher than that previously observed using fetal-tissue-derived OPCs, and no tumors from these grafts were noted as long as 9 months after transplant. These results suggest the potential utility of hiPSC-derived OPCs in treating disorders of myelin loss. C1 [Wang, Su; Bates, Janna; Li, Xiaojie; Schanz, Steven; Chandler-Militello, Devin; Levine, Corri; Windrem, Martha; Goldman, Steven A.] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA. [Wang, Su; Bates, Janna; Li, Xiaojie; Schanz, Steven; Chandler-Militello, Devin; Levine, Corri; Windrem, Martha; Goldman, Steven A.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 USA. [Maherali, Nimet; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Studer, Lorenz] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA. RP Goldman, SA (reprint author), Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA. EM steven_goldman@urmc.rochester.edu OI Levine, Corri/0000-0003-0405-5191 FU New York State Stem Cell Science (NYSTEM); National Multiple Sclerosis Society; NIH [R01NS75345, R01NS39559]; G. Harold and Leila Y. Mathers Charitable Foundation; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX This work was supported by New York State Stem Cell Science (NYSTEM); the National Multiple Sclerosis Society; NIH grants R01NS75345 and R01NS39559; the G. Harold and Leila Y. Mathers Charitable Foundation; and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. We thank Karen Bentley and Gayle Schneider for their assistance in electron microscopy. NR 29 TC 155 Z9 159 U1 9 U2 43 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD FEB 7 PY 2013 VL 12 IS 2 BP 252 EP 264 DI 10.1016/j.stem.2012.12.002 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VB UT WOS:000329569300015 PM 23395447 ER PT J AU Paccez, JD Vasques, GJ Correa, RG Vasconcellos, JF Duncan, K Gu, X Bhasin, M Libermann, TA Zerbini, LF AF Paccez, J. D. Vasques, G. J. Correa, R. G. Vasconcellos, J. F. Duncan, K. Gu, X. Bhasin, M. Libermann, T. A. Zerbini, L. F. TI The receptor tyrosine kinase Ax1 is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target SO ONCOGENE LA English DT Article DE tyrosine kinase receptor; Ax1; prostate cancer; proliferation; NF-kappa B; IL-6 ID NF-KAPPA-B; ARREST-SPECIFIC GENE-6; BREAST-CANCER; PROLONGS SURVIVAL; ENDOTHELIAL-CELLS; CARCINOMA CELLS; ACTIVATION; PATHWAY; EXPRESSION; GAS6 AB Deregulation of the receptor tyrosine kinase Ax1 has been implicated in the progression of several human cancers. However, the role of Ax1 in prostate cancer remains poorly understood, and the therapeutic efficacy of Ax1 targeting remains untested. In this report we identified Ax1 as a new therapeutic target for prostate cancer. Ax1 is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Ax1 gene expression strongly inhibits proliferation, migration, invasion and tumor growth. Furthermore, inhibition of Ax1 expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-kappa B pathway. Additionally, blockage of Ax1 expression leads to inhibition of Akt, IKK alpha and I kappa B alpha phosphorylation, increasing I kappa B alpha expression and stability. Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Ax1 knockdown cells restores Akt activity and proliferation. Taken together, our results establish an unambiguous role for Ax1 in prostate cancer tumorigenesis with implications for prostate cancer treatment. Oncogene (2013) 32, 689-698; doi:10.1038/onc.2012.89; published online 12 March 2012 C1 [Paccez, J. D.; Vasques, G. J.; Duncan, K.; Zerbini, L. F.] Int Ctr Genet Engn & Biotechnol, Canc Genom Grp, Cape Town, South Africa. [Paccez, J. D.; Zerbini, L. F.] Univ Cape Town, Div Med Biochem, ZA-7925 Cape Town, South Africa. [Correa, R. G.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Vasconcellos, J. F.; Gu, X.; Bhasin, M.; Libermann, T. A.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA. [Vasconcellos, J. F.; Gu, X.; Bhasin, M.; Libermann, T. A.] Harvard Univ, Sch Med, Boston, MA USA. RP Zerbini, LF (reprint author), Int Ctr Genet Engn & Biotechnol, Canc Genom Grp, Cape Town, South Africa. EM luiz.zerbini@uct.ac.za RI Correa, Ricardo/G-7613-2012; Zerbini, Luiz /B-7720-2015; Paccez, Juliano/K-8560-2012 OI Correa, Ricardo/0000-0001-6940-7034; Paccez, Juliano/0000-0002-1086-4588 FU ICGEB post-doctoral fellowship; CAPES international fellowship; Department of Defense [PC051217]; NIH [1RO1 CA85467]; Prostate Cancer Foundation FX JDP is recipient of the ICGEB post-doctoral fellowship. JFV is recipient of CAPES international fellowship. This study was supported by the Department of Defense grant PC051217 (LFZ), NIH grants 1RO1 CA85467 (TAL) and the Prostate Cancer Foundation (TAL). NR 50 TC 36 Z9 39 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 7 PY 2013 VL 32 IS 6 BP 689 EP 698 DI 10.1038/onc.2012.89 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 101AF UT WOS:000315746700003 PM 22410775 ER PT J AU Beunders, G Voorhoeve, E Golzio, C Pardo, LM Rosenfeld, JA Talkowski, ME Simonic, I Lionel, AC Vergult, S Pyatt, RE van de Kamp, J Nieuwint, A Weiss, MM Rizzu, P Verwer, LENI van Spaendonk, RML Shen, YP Wu, BL Yu, TT Yu, YG Chiang, C Gusella, JF Lindgren, AM Morton, CC van Binsbergen, E Bulk, S van Rossem, E Vanakker, O Armstrong, R Park, SM Greenhalgh, L Maye, U Neill, NJ Abbott, KM Sell, S Ladda, R Farber, DM Bader, PI Cushing, T Drautz, JM Konczal, L Nash, P de Los Reyes, E Carter, MT Hopkins, E Marshall, CR Osborne, LR Gripp, KW Thrush, DL Hashimoto, S Gastier-Foster, JM Astbury, C Ylstra, B Meijers-Heijboer, H Posthuma, D Menten, B Mortier, G Scherer, SW Eichler, EE Girirajan, S Katsanis, N Groffen, AJ Sistermans, EA AF Beunders, Gea Voorhoeve, Els Golzio, Christelle Pardo, Luba M. Rosenfeld, Jill A. Talkowski, Michael E. Simonic, Ingrid Lionel, Anath C. Vergult, Sarah Pyatt, Robert E. van de Kamp, Jiddeke Nieuwint, Aggie Weiss, Marjan M. Rizzu, Patrizia Verwer, Lucilla E. N. I. van Spaendonk, Rosalina M. L. Shen, Yiping Wu, Bai-lin Yu, Tingting Yu, Yongguo Chiang, Colby Gusella, James F. Lindgren, Amelia M. Morton, Cynthia C. van Binsbergen, Ellen Bulk, Saskia van Rossem, Els Vanakker, Olivier Armstrong, Ruth Park, Soo-Mi Greenhalgh, Lynn Maye, Una Neill, Nicholas J. Abbott, Kristin M. Sell, Susan Ladda, Roger Farber, Darren M. Bader, Patricia I. Cushing, Tom Drautz, Joanne M. Konczal, Laura Nash, Patricia de Los Reyes, Emily Carter, Melissa T. Hopkins, Elizabeth Marshall, Christian R. Osborne, Lucy R. Gripp, Karen W. Thrush, Devon Lamb Hashimoto, Sayaka Gastier-Foster, Julie M. Astbury, Caroline Ylstra, Bauke Meijers-Heijboer, Hanne Posthuma, Danielle Menten, Bjoern Mortier, Geert Scherer, Stephen W. Eichler, Evan E. Girirajan, Santhosh Katsanis, Nicholas Groffen, Alexander J. Sistermans, Erik A. TI Exonic Deletions in AUTS2 Cause a Syndromic Form of Intellectual Disability and Suggest a Critical Role for the C Terminus SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRANSLOCATION BREAKPOINT; MUTATIONS; AUTISM; ABNORMALITIES; GENERATION; PHENOTYPE; DATABASE; GENES AB Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3' AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future. C1 [Beunders, Gea; Voorhoeve, Els; Pardo, Luba M.; van de Kamp, Jiddeke; Nieuwint, Aggie; Weiss, Marjan M.; Rizzu, Patrizia; Verwer, Lucilla E. N. I.; van Spaendonk, Rosalina M. L.; Meijers-Heijboer, Hanne; Posthuma, Danielle; Groffen, Alexander J.; Sistermans, Erik A.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands. [Golzio, Christelle; Katsanis, Nicholas] Duke Univ, Med Ctr, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Rosenfeld, Jill A.; Neill, Nicholas J.] Perkin Elmer, Signature Genom Labs, Spokane, WA 99207 USA. [Talkowski, Michael E.; Shen, Yiping; Chiang, Colby; Gusella, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Dept Genet, Boston, MA 02114 USA. [Talkowski, Michael E.; Shen, Yiping; Chiang, Colby; Gusella, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Dept Neurol, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.; Morton, Cynthia C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Simonic, Ingrid; Armstrong, Ruth; Park, Soo-Mi; Abbott, Kristin M.] Natl Hlth Serv Fdn Trust, Cambridge Univ Hosp, Addenbrookes Hosp, E Anglian Med Genet Serv, Cambridge CB2 0QQ, England. [Lionel, Anath C.; Marshall, Christian R.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Marshall, Christian R.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Vergult, Sarah; Vanakker, Olivier; Menten, Bjoern] Univ Hosp Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Pyatt, Robert E.; Thrush, Devon Lamb; Hashimoto, Sayaka; Gastier-Foster, Julie M.; Astbury, Caroline] Nationwide Childrens Hosp, Columbus, OH 43205 USA. [Pyatt, Robert E.; Gastier-Foster, Julie M.; Astbury, Caroline] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Shen, Yiping; Wu, Bai-lin; Yu, Tingting] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02114 USA. [Shen, Yiping; Yu, Tingting; Yu, Yongguo] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200025, Peoples R China. [Wu, Bai-lin] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China. [Wu, Bai-lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Lindgren, Amelia M.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lindgren, Amelia M.; Morton, Cynthia C.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [van Binsbergen, Ellen; Bulk, Saskia] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 AB Utrecht, Netherlands. [van Rossem, Els] Onze Lieve Vrouwe Ziekenhuis, B-9300 Aalst, Belgium. [Greenhalgh, Lynn; Maye, Una] Royal Liverpool Childrens Hosp, Liverpool L12 2AP, Merseyside, England. [Sell, Susan; Ladda, Roger] Penn State Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Farber, Darren M.] Univ Louisville, Dept Neurol, Louisville, KY 40222 USA. [Bader, Patricia I.] NE Indiana Genet Counseling Ctr, Ft Wayne, IN 46804 USA. [Cushing, Tom; Drautz, Joanne M.] Univ New Mexico, Dept Pediat, Pediat Genet Div, Albuquerque, NM 87131 USA. [Konczal, Laura] Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. [Nash, Patricia] Nationwide Childrens Hosp, Dept Behav Pediat, Columbus, OH 43205 USA. [de Los Reyes, Emily] Ohio State Univ, Dept Pediat & Neurol, Columbus, OH 43210 USA. [Carter, Melissa T.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Hopkins, Elizabeth; Gripp, Karen W.] Alfred I duPont Hosp Children, Div Med Genet, Wilmington, DE 19803 USA. [Osborne, Lucy R.] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. [Osborne, Lucy R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Thrush, Devon Lamb] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Ylstra, Bauke] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. [Posthuma, Danielle; Groffen, Alexander J.] Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [Mortier, Geert] Univ Antwerp, Dept Med Genet, B-2650 Edegem, Belgium. [Eichler, Evan E.; Girirajan, Santhosh] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.; Girirajan, Santhosh] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Girirajan, Santhosh] Penn State Univ, Dept Biochem & Mol Biol, Dept Anthropol, University Pk, PA 16803 USA. RP Sistermans, EA (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands. EM e.sistermans@vumc.nl RI Mortier, Geert/D-2542-2012; Scherer, Stephen /B-3785-2013; Katsanis, Nicholas/E-1837-2012; Groffen, Alexander/C-1118-2009; Astbury, Caroline/E-2665-2011; Ylstra, Bauke/D-2906-2012; OI yu, yongguo/0000-0002-4472-0910; Katsanis, Nicholas/0000-0002-2480-0171; Scherer, Stephen /0000-0002-8326-1999; Groffen, Alexander/0000-0003-0046-4027; Ylstra, Bauke/0000-0001-9479-3010; Menten, Bjorn/0000-0001-8182-659X; Golzio, Christelle/0000-0002-4420-3921; Sistermans, Erik/0000-0001-7187-4563; Chiang, Colby/0000-0002-4113-6065 FU Wellcome Trust [076113, 085475]; National Institutes of Health [GM061354, HD065286, MH095867]; American Heart Association [11POST7160006]; Distinguished Brumley Professorship FX The authors would like to thank all patients and their families for their major contribution; without them, we would not have been able to describe this syndrome. We thank Marjolein van de Mespel, Desiree Linders, Stefan Strijbis, Amanda Clarkson, and Carrie Hanscom for their contribution to the laboratory work in this project and Shahrin Pereira for clinical coordination. This study made use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk. Funding for this project was provided by the Wellcome Trust under awards 076113 and 085475, as well as by the National Institutes of Health (GM061354, HD065286, and MH095867), the American Heart Association (11POST7160006), and a Distinguished Brumley Professorship to N.K. Evan Eichler is a Howards Hughes Medical Institute investigator. The authors thank Klaas Kok for making available the control data of The Low-Lands Consortium for this study and for developing the custom design of the 180K Agilent oligo array used in The Netherlands. We acknowledge Soheil Shams from Bio-Discovery for his help with processing the different array data files. J.A.R. and N.J.N. are employees of Signature Genomic Laboratories, a subsidiary of PerkinElmer, and E.E.E. is on the scientific advisory boards for Pacific Biosciences, SynapDx, and DNAnexus. NR 24 TC 46 Z9 47 U1 0 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB 7 PY 2013 VL 92 IS 2 BP 210 EP 220 DI 10.1016/j.ajhg.2012.12.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 093GL UT WOS:000315179600005 PM 23332918 ER PT J AU Borissoff, JI Otten, JJT Heeneman, S Leenders, P van Oerle, R Soehnlein, O Loubele, STBG Hamulyak, K Hackeng, TM Daemen, MJAP Degen, JL Weiler, H Esmon, CT van Ryn, J Biessen, EAL Spronk, HMH ten Cate, H AF Borissoff, Julian I. Otten, Jeroen J. T. Heeneman, Sylvia Leenders, Peter van Oerle, Rene Soehnlein, Oliver Loubele, Sarah T. B. G. Hamulyak, Karly Hackeng, Tilman M. Daemen, Mat J. A. P. Degen, Jay L. Weiler, Hartmut Esmon, Charles T. van Ryn, Joanne Biessen, Erik A. L. Spronk, Henri M. H. ten Cate, Hugo TI Genetic and Pharmacological Modifications of Thrombin Formation in Apolipoprotein E-deficient Mice Determine Atherosclerosis Severity and Atherothrombosis Onset in a Neutrophil-Dependent Manner SO PLOS ONE LA English DT Article ID SUDDEN CORONARY DEATH; COLONY-STIMULATING FACTOR; PLAQUE STABILITY; P-SELECTIN; INFLAMMATION; ATHEROGENESIS; COAGULATION; MECHANISMS; DISEASE; ACTIVATION AB Background: Variations in the blood coagulation activity, determined genetically or by medication, may alter atherosclerotic plaque progression, by influencing pleiotropic effects of coagulation proteases. Published experimental studies have yielded contradictory findings on the role of hypercoagulability in atherogenesis. We therefore sought to address this matter by extensively investigating the in vivo significance of genetic alterations and pharmacologic inhibition of thrombin formation for the onset and progression of atherosclerosis, and plaque phenotype determination. Methodology/Principal Findings: We generated transgenic atherosclerosis-prone mice with diminished coagulant or hypercoagulable phenotype and employed two distinct models of atherosclerosis. Gene-targeted 50% reduction in prothrombin (FII-/WT:ApoE(-/-)) was remarkably effective in limiting disease compared to control ApoE(-/-) mice, associated with significant qualitative benefits, including diminished leukocyte infiltration, altered collagen and vascular smooth muscle cell content. Genetically-imposed hypercoagulability in TMPro/Pro:ApoE(-/-) mice resulted in severe atherosclerosis, plaque vulnerability and spontaneous atherothrombosis. Hypercoagulability was associated with a pronounced neutrophilia, neutrophil hyper-reactivity, markedly increased oxidative stress, neutrophil intraplaque infiltration and apoptosis. Administration of either the synthetic specific thrombin inhibitor Dabigatran etexilate, or recombinant activated protein C (APC), counteracted the pro-inflammatory and pro-atherogenic phenotype of pro-thrombotic TMPro/Pro:ApoE(-/-) mice. Conclusions/Significance: We provide new evidence highlighting the importance of neutrophils in the coagulation-inflammation interplay during atherogenesis. Our findings reveal that thrombin-mediated proteolysis is an unexpectedly powerful determinant of atherosclerosis in multiple distinct settings. These studies suggest that selective anticoagulants employed to prevent thrombotic events may also be remarkably effective in clinically impeding the onset and progression of cardiovascular disease. C1 [Borissoff, Julian I.; Leenders, Peter; van Oerle, Rene; Loubele, Sarah T. B. G.; Hamulyak, Karly; Spronk, Henri M. H.; ten Cate, Hugo] Maastricht Univ, Med Ctr, Lab Clin Thrombosis & Hemostasis, Dept Internal Med,Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [Borissoff, Julian I.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA. [Borissoff, Julian I.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Otten, Jeroen J. T.; Heeneman, Sylvia; Daemen, Mat J. A. P.; Biessen, Erik A. L.] Maastricht Univ, Cardiovasc Res Inst Maastricht, Expt Vasc Pathol Res Grp, Dept Pathol, Maastricht, Netherlands. [Soehnlein, Oliver] Rhein Westfal TH Aachen, Fac Med, Inst Cardiovasc Mol Res, Aachen, Germany. [Hackeng, Tilman M.] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Biochem, Med Ctr, Maastricht, Netherlands. [Degen, Jay L.] Univ Cincinnati, Coll Med, Childrens Hosp Res Fdn, Cincinnati, OH USA. [Weiler, Hartmut] Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53233 USA. [Esmon, Charles T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Esmon, Charles T.] Howard Hughes Med Inst, Oklahoma City, OK USA. [van Ryn, Joanne] Boehringer Ingelheim Pharma GmbH & Co KG, Dept CardioMetab Dis Res, Biberach, Germany. RP Borissoff, JI (reprint author), Maastricht Univ, Med Ctr, Lab Clin Thrombosis & Hemostasis, Dept Internal Med,Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. EM j.ilcheff@maastrichtuniversity.nl OI ten Cate, Hugo/0000-0001-7796-4463 FU European Commission [MEST-CT-2005-020706]; SenterNovem grant; Maastricht University; Netherlands Organization for Scientific Research (NWO) [825.11.019]; Deutsche Forschungsgemeinschaft [SO876/3-1, SO876/4-1]; Gutenberg Research College Fellowship (Gutenberg University, Mainz, Germany); Bayer; Boehringer Ingelheim; GlaxoSmithKline; Leo Pharma FX Boehringer Ingelheim GmbH provided Dabigatran etexilate-supplemented and placebo diets. This study was supported by a Marie Curie fellowship (MEST-CT-2005-020706) from the European Commission (to Dr. J.I. Borissoff) and a SenterNovem grant (to Cardiovascular Research Institute Maastricht (CARIM)). Dr. J.I. Borissoff is a recipient of a Kootstra Talent Fellowship (2011) from Maastricht University and is supported by a Rubicon fellowship (825.11.019), granted by the Netherlands Organization for Scientific Research (NWO). Dr. Oliver Soehnlein is supported by the Deutsche Forschungsgemeinschaft (SO876/3-1 and SO876/4-1). Dr. Hugo ten Cate is sponsored by a Gutenberg Research College Fellowship (Gutenberg University, Mainz, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors have the following interests. Boehringer Ingelheim GmbH provided Dabigatran etexilate-supplemented and placebo diets for this study and is the employer of Joanne van Ryn. Dr. ten Cate has received speaker fees from Bayer, Boehringer Ingelheim, GlaxoSmithKline and Leo Pharma. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. NR 55 TC 36 Z9 36 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 7 PY 2013 VL 8 IS 2 AR e55784 DI 10.1371/journal.pone.0055784 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092XV UT WOS:000315157200063 PM 23409043 ER PT J AU Plovanich, M Bogorad, RL Sancak, Y Kamer, KJ Strittmatter, L Li, AA Girgis, HS Kuchimanchi, S De Groot, J Speciner, L Taneja, N Oshea, J Koteliansky, V Mootha, VK AF Plovanich, Molly Bogorad, Roman L. Sancak, Yasemin Kamer, Kimberli J. Strittmatter, Laura Li, Andrew A. Girgis, Hany S. Kuchimanchi, Satya De Groot, Jack Speciner, Lauren Taneja, Nathan Oshea, Jonathan Koteliansky, Victor Mootha, Vamsi K. TI MICU2, a Paralog of MICU1, Resides within the Mitochondrial Uniporter Complex to Regulate Calcium Handling SO PLOS ONE LA English DT Article ID RAT KIDNEY MITOCHONDRIA; CA2+ UPTAKE; ESSENTIAL COMPONENT; RNAI THERAPEUTICS; RESPIRATION; METABOLISM; DELIVERY; PROTEIN; MCU; OSCILLATIONS AB Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel. C1 [Plovanich, Molly; Sancak, Yasemin; Kamer, Kimberli J.; Strittmatter, Laura; Li, Andrew A.; Girgis, Hany S.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Plovanich, Molly; Sancak, Yasemin; Kamer, Kimberli J.; Strittmatter, Laura; Li, Andrew A.; Girgis, Hany S.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Plovanich, Molly; Sancak, Yasemin; Kamer, Kimberli J.; Strittmatter, Laura; Li, Andrew A.; Girgis, Hany S.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Plovanich, Molly; Sancak, Yasemin; Kamer, Kimberli J.; Strittmatter, Laura; Li, Andrew A.; Girgis, Hany S.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Bogorad, Roman L.; Koteliansky, Victor] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kuchimanchi, Satya; De Groot, Jack; Speciner, Lauren; Taneja, Nathan; Oshea, Jonathan] Alnylam Pharmaceut Inc, Cambridge, MA USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu OI Kamer, Kimberli/0000-0001-8728-7793 FU National Institutes of Health [GM0077465, DK080261]; Alnylam FX This work was supported by grants from the National Institutes of Health (GM0077465, DK080261) awarded to VKM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Please note that in this paper, the authors' academic laboratory (based at Massachusetts General Hospital/Harvard Medical School) collaborated with Alnylam Pharmaceuticals (co-authors include JDG, L. Speciner, NT, JO, VK). As employees, they received compensation/stock from Alnylam. The authors do not believe that the fact that they are employees of a company, receiving salary/equity from this company, represents a competing interest that compromises the objectivity of the work. This does not alter the authors' adherence to all the PLOS ONE policies on data sharing and materials. NR 32 TC 89 Z9 97 U1 1 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 7 PY 2013 VL 8 IS 2 AR e55785 DI 10.1371/journal.pone.0055785 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092XV UT WOS:000315157200064 PM 23409044 ER PT J AU Fulzele, K Krause, DS Panaroni, C Saini, V Barry, KJ Liu, XL Lotinun, S Baron, R Bonewald, L Feng, JQ Chen, M Weinstein, LS Wu, JY Kronenberg, HM Scadden, DT Pajevic, PD AF Fulzele, Keertik Krause, Daniela S. Panaroni, Cristina Saini, Vaibhav Barry, Kevin J. Liu, Xiaolong Lotinun, Sutada Baron, Roland Bonewald, Lynda Feng, Jian Q. Chen, Min Weinstein, Lee S. Wu, Joy Y. Kronenberg, Henry M. Scadden, David T. Pajevic, Paola Divieti TI Myelopoiesis is regulated by osteocytes through Gs alpha-dependent signaling SO BLOOD LA English DT Article ID STEM-CELL NICHE; HEMATOPOIETIC STEM; BONE-FORMATION; G-PROTEIN; PROGENITOR CELLS; RECEPTOR; OSTEOBLASTS; SCLEROSTIN; MARROW; DIFFERENTIATION AB Hematopoietic progenitors are regulated in their respective niches by cells of the bone marrow microenvironment. The bone marrow microenvironment is composed of a variety of cell types, and the relative contribution of each of these cells for hematopoietic lineage maintenance has remained largely unclear. Osteocytes, the most abundant yet least understood cells in bone, are thought to initiate adaptive bone remodeling responses via osteoblasts and osteoclasts. Here we report that these cells regulate hematopoiesis, constraining myelopoiesis through a Gs alpha-mediated mechanism that affects G-CSF production. Mice lacking Gs alpha in osteocytes showed a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. This hematopoietic phenomenon was neither intrinsic to the hematopoietic cells nor dependent on osteoblasts but was a consequence of an altered bone marrow microenvironment imposed by Gs alpha deficiency in osteocytes. Conditioned media from osteocyte-enriched bone explants significantly increased myeloid colony formation in vitro, which was blocked by G-CSF-neutralizing antibody, indicating a critical role of osteocyte-derived G-CSF in the myeloid expansion. (Blood. 2013;121(6):930-939) C1 [Fulzele, Keertik; Panaroni, Cristina; Saini, Vaibhav; Barry, Kevin J.; Liu, Xiaolong; Baron, Roland; Wu, Joy Y.; Kronenberg, Henry M.; Pajevic, Paola Divieti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Krause, Daniela S.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Bonewald, Lynda] Univ Missouri, Dept Oral Biol, Kansas City, MO 64110 USA. [Feng, Jian Q.] Baylor Coll Dent, Dept Biomed Sci, Texas A&M Hlth Sci Ctr, Dallas, TX 75246 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Pajevic, PD (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1101, Boston, MA 02114 USA. EM divieti@helix.mgh.harvard.edu FU National Institutes of Health [AR060221, DK079161, K08CA138916]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Harvard Stem Cell Institute FX This work was supported by the National Institutes of Health (grants AR060221 and DK079161, P. D. P.; grant K08CA138916, D. S. K.), the Intramural Research Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (L. S. W.), and the Harvard Stem Cell Institute (J.Y.W.). NR 33 TC 46 Z9 46 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 7 PY 2013 VL 121 IS 6 BP 930 EP 939 DI 10.1182/blood-2012-06-437160 PG 10 WC Hematology SC Hematology GA 088WO UT WOS:000314868800014 PM 23160461 ER PT J AU Duerschmied, D Suidan, GL Demers, M Herr, N Carbo, C Brill, A Cifuni, SM Mauler, M Cicko, S Bader, M Idzko, M Bode, C Wagner, DD AF Duerschmied, Daniel Suidan, Georgette L. Demers, Melanie Herr, Nadine Carbo, Carla Brill, Alexander Cifuni, Stephen M. Mauler, Maximilian Cicko, Sanja Bader, Michael Idzko, Marco Bode, Christoph Wagner, Denisa D. TI Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; SELECTIN-DEFICIENT MICE; SMOOTH-MUSCLE-CELLS; P-SELECTIN; PULMONARY-HYPERTENSION; ENDOTHELIAL-CELLS; MAST-CELLS; RECEPTOR; 5-HYDROXYTRYPTAMINE; PERMEABILITY AB The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1-deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1(-/-) mice. The velocity of rolling leukocytes was higher in Tph1(-/-) mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1(-/-) mice. Diminished rolling in Tph1(-/-) mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1(-/-) mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1(-/-) mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. (Blood. 2013;121(6):1008-1015) C1 [Duerschmied, Daniel; Suidan, Georgette L.; Demers, Melanie; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA. [Duerschmied, Daniel; Suidan, Georgette L.; Demers, Melanie; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Duerschmied, Daniel; Suidan, Georgette L.; Demers, Melanie; Carbo, Carla; Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Duerschmied, Daniel; Herr, Nadine; Mauler, Maximilian; Bode, Christoph] Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol 1, D-79106 Freiburg, Germany. [Cicko, Sanja; Idzko, Marco] Univ Med Ctr Freiburg, Dept Pneumol, Freiburg, Germany. [Bader, Michael] Max Delbruck Ctr Mol Med, Berlin, Germany. RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Cir,3rd Fl, Boston, MA 02115 USA. EM daniel.duerschmied@uniklinik-freiburg.de; denisa.wagner@childrens.harvard.edu OI Bader, Michael/0000-0003-4780-4164 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL095091, R01 HL041002]; Deutsche Forschungsgemeinschaft [DU 1190/3-1] FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grants R01 HL095091 (D. D. W.) and R01 HL041002 (D. D. W.). D. D. was supported by a fellowship of the Deutsche Forschungsgemeinschaft (DU 1190/3-1). NR 50 TC 54 Z9 54 U1 1 U2 26 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 7 PY 2013 VL 121 IS 6 BP 1008 EP 1015 DI 10.1182/blood-2012-06-437392 PG 8 WC Hematology SC Hematology GA 088WO UT WOS:000314868800022 PM 23243271 ER PT J AU Metallo, CM Vander Heiden, MG AF Metallo, Christian M. Vander Heiden, Matthew G. TI Understanding Metabolic Regulation and Its Influence on Cell Physiology SO MOLECULAR CELL LA English DT Review ID MITOCHONDRIAL PYRUVATE CARRIER; C-13 MAGNETIC-RESONANCE; PROTEIN-KINASE; GLUTAMINE-METABOLISM; GLUCOSE-METABOLISM; FLUX ANALYSIS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; REDUCTIVE CARBOXYLATION; HISTONE DEMETHYLATION; DEHYDROGENASE KINASE AB Metabolism impacts all cellular functions and plays a fundamental role in biology. In the last century, our knowledge of metabolic pathway architecture and the genomic landscape of disease has increased exponentially. Combined with these insights, advances in analytical methods for quantifying metabolites and systems approaches to analyze these data now provide powerful tools to study metabolic regulation. Here we review the diverse mechanisms cells use to adapt metabolism to specific physiological states and discuss how metabolic flux analyses can be applied to identify important regulatory nodes to understand normal and pathological cell physiology. C1 [Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Metallo, CM (reprint author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. EM cmetallo@ucsd.edu; mvh@mit.edu FU American Cancer Society Institutional Research Grant [70-002]; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Smith Family Foundation; National Cancer Institute FX We thank members of the Metallo and Vander Heiden laboratories for comments and Brooke Bevis for help generating the figures. C.M.M. is supported by the American Cancer Society Institutional Research Grant 70-002. M.G.V.H. is supported by the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, the Smith Family Foundation, and the National Cancer Institute. NR 98 TC 66 Z9 68 U1 6 U2 70 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD FEB 7 PY 2013 VL 49 IS 3 BP 388 EP 398 DI 10.1016/j.molcel.2013.01.018 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087VO UT WOS:000314792500002 PM 23395269 ER PT J AU Fang, R Chen, F Dong, ZH Hu, D Barbera, AJ Clark, EA Fang, J Yang, Y Mei, PC Rutenberg, M Li, Z Zhang, Y Xu, YW Yang, HR Wang, P Simon, MD Zhou, QJ Li, J Marynick, MP Li, XT Lu, HJ Kaiser, UB Kingston, RE Xu, YH Shi, YJG AF Fang, Rui Chen, Fei Dong, Zhenghong Hu, Di Barbera, Andrew J. Clark, Erin A. Fang, Jian Yang, Ying Mei, Pinchao Rutenberg, Michael Li, Ze Zhang, Ying Xu, Youwei Yang, Huirong Wang, Ping Simon, Matthew D. Zhou, Qiongjie Li, Jing Marynick, Mark P. Li, Xiaotian Lu, Haojie Kaiser, Ursula B. Kingston, Robert E. Xu, Yanhui Shi, Yujiang Geno TI LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation SO MOLECULAR CELL LA English DT Article ID HISTONE LYSINE DEMETHYLASES; LSD1; RECOGNITION; DISEASE; CANCER; DOMAIN; MARKS; TRANSCRIPTION; METHYLATION; EPIGENETICS AB Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 angstrom, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214-225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation. C1 [Fang, Rui; Hu, Di; Barbera, Andrew J.; Clark, Erin A.; Mei, Pinchao; Rutenberg, Michael; Zhou, Qiongjie; Li, Jing; Marynick, Mark P.; Kaiser, Ursula B.; Shi, Yujiang Geno] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. [Fang, Rui; Hu, Di; Barbera, Andrew J.; Clark, Erin A.; Mei, Pinchao; Rutenberg, Michael; Zhou, Qiongjie; Li, Jing; Marynick, Mark P.; Kaiser, Ursula B.; Shi, Yujiang Geno] Brigham & Womens Hosp, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Fang, Rui; Hu, Di; Barbera, Andrew J.; Clark, Erin A.; Mei, Pinchao; Rutenberg, Michael; Zhou, Qiongjie; Li, Jing; Marynick, Mark P.; Kaiser, Ursula B.; Shi, Yujiang Geno] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Fei; Dong, Zhenghong; Hu, Di; Fang, Jian; Yang, Ying; Li, Ze; Zhang, Ying; Xu, Youwei; Yang, Huirong; Wang, Ping; Lu, Haojie; Xu, Yanhui; Shi, Yujiang Geno] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Zhang, Ying; Lu, Haojie] Fudan Univ, Dept Chem, Shanghai 200032, Peoples R China. [Chen, Fei; Dong, Zhenghong; Fang, Jian; Yang, Ying; Li, Ze; Xu, Youwei; Yang, Huirong; Wang, Ping; Xu, Yanhui] Fudan Univ, State Key Lab Genet Engn, Shanghai 200032, Peoples R China. [Zhou, Qiongjie; Li, Xiaotian] Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200032, Peoples R China. [Shi, Yujiang Geno] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China. [Simon, Matthew D.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Xu, YH (reprint author), Fudan Univ, Inst Biomed Sci, 130 Dong An Rd, Shanghai 200032, Peoples R China. EM xuyh@fudan.edu.cn; yujiang_shi@hms.harvard.edu OI Mei, Pinchao/0000-0002-1564-0372; Li, Jing/0000-0001-7699-4249 FU National Institutes of Health [5R01GM078458]; Brigham and Women's Hospital Funds to Sustain Research Excellence; National Basic Research Program of China [2011CB965300, 2009CB918600]; National Natural Science Foundation of China [81130047, 31270779, 31030019, 11079016, 30870493]; Fok Ying Tung Education Foundation [20090071220012] FX We thank staff members of beamline BL17U at SSRF for assistance in data collection and staff members of the Biomedical Core Facility, Fudan University for mass spectrometry analyses. We thank James Chou, Paco Kang, and Lisa Schwartz for critical reading of the manuscript. This work was supported by grants from the National Institutes of Health (5R01GM078458) and Brigham and Women's Hospital Funds to Sustain Research Excellence to Y.G.S., and the National Basic Research Program of China (2011CB965300 and 2009CB918600), the National Natural Science Foundation of China (81130047, 31270779, 31030019, 11079016, and 30870493), and the Fok Ying Tung Education Foundation (20090071220012). NR 47 TC 28 Z9 28 U1 1 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD FEB 7 PY 2013 VL 49 IS 3 BP 558 EP 570 DI 10.1016/j.molcel.2012.11.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087VO UT WOS:000314792500018 PM 23260659 ER PT J AU Kesselheim, JC Cassel, CK AF Kesselheim, Jennifer C. Cassel, Christine K. TI Service: An Essential Component of Graduate Medical Education SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kesselheim, Jennifer C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kesselheim, Jennifer C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Cassel, Christine K.] Amer Board Internal Med, Philadelphia, PA USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 5 TC 8 Z9 9 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 7 PY 2013 VL 368 IS 6 BP 500 EP 501 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 083VU UT WOS:000314494100014 PM 23388001 ER PT J AU Thanassoulis, G Campbell, CY Owens, DS Smith, JG Smith, AV Peloso, GM Kerr, KF Pechlivanis, S Budoff, MJ Harris, TB Malhotra, R O'Brien, KD Kamstrup, PR Nordestgaard, BG Tybjaerg-Hansen, A Allison, MA Aspelund, T Criqui, MH Heckbert, SR Hwang, SJ Liu, YM Sjogren, M van der Pals, J Kalsch, H Muhleisen, TW Nothen, MM Cupples, LA Caslake, M Di Angelantonio, E Danesh, J Rotter, JI Sigurdsson, S Wong, Q Erbel, R Kathiresan, S Melander, O Gudnason, V O'Donnell, CJ Post, WS AF Thanassoulis, George Campbell, Catherine Y. Owens, David S. Smith, J. Gustav Smith, Albert V. Peloso, Gina M. Kerr, Kathleen F. Pechlivanis, Sonali Budoff, Matthew J. Harris, Tamara B. Malhotra, Rajeev O'Brien, Kevin D. Kamstrup, Pia R. Nordestgaard, Borge G. Tybjaerg-Hansen, Anne Allison, Matthew A. Aspelund, Thor Criqui, Michael H. Heckbert, Susan R. Hwang, Shih-Jen Liu, Yongmei Sjogren, Marketa van der Pals, Jesper Kaelsch, Hagen Muehleisen, Thomas W. Noethen, Markus M. Cupples, L. Adrienne Caslake, Muriel Di Angelantonio, Emanuele Danesh, John Rotter, Jerome I. Sigurdsson, Sigurdur Wong, Quenna Erbel, Raimund Kathiresan, Sekar Melander, Olle Gudnason, Vilmundur O'Donnell, Christopher J. Post, Wendy S. CA CHARGE Extracoronary Calcium Worki TI Genetic Associations with Valvular Calcification and Aortic Stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY CALCIUM; RISK-FACTORS; VALVE CALCIFICATION; MYOCARDIAL-INFARCTION; LP(A) LIPOPROTEIN; HEART-DISEASE; LONG-TERM; DESIGN; ATHEROSCLEROSIS AB Background Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. Methods We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. Results One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P = 9.0x10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P = 1.5x10(-8) and P = 1.8x10(-8), respectively), but the findings were not replicated consistently. Conclusions Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.) C1 [Thanassoulis, George] McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ, Canada. [Thanassoulis, George] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA. [Thanassoulis, George; Peloso, Gina M.; Hwang, Shih-Jen; Cupples, L. Adrienne; Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Peloso, Gina M.; Malhotra, Rajeev; Kathiresan, Sekar; O'Donnell, Christopher J.] Boston Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02118 USA. [Campbell, Catherine Y.; Post, Wendy S.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Liu, Yongmei] Wake Forest Sch Med, Winston Salem, NC USA. [Kerr, Kathleen F.; Wong, Quenna] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Owens, David S.; O'Brien, Kevin D.] Univ Washington, Dept Med, Seattle, WA USA. [Smith, Albert V.; Aspelund, Thor; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Caslake, Muriel] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Di Angelantonio, Emanuele; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Smith, J. Gustav] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Smith, J. Gustav; van der Pals, Jesper] Lund Univ, Dept Cardiol, Lund, Sweden. [Sjogren, Marketa; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Pechlivanis, Sonali] Univ Essen Gesamthsch, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Kaelsch, Hagen; Erbel, Raimund] W German Heart Ctr, Dept Cardiol, Essen, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Noethen, Markus M.] Univ Bonn, German Ctr Neurodegenerat Dis, Bonn, Germany. [Kamstrup, Pia R.; Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Nordestgaard, Borge G.; Tybjaerg-Hansen, Anne] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. RP Post, WS (reprint author), Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM wpost@jhmi.edu RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; Kerr, Kathleen/A-2893-2013; OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Cupples, L. Adrienne/0000-0003-0273-7965; Di Angelantonio, Emanuele/0000-0001-8776-6719; Owens, David/0000-0002-7293-9688; Nothen, Markus/0000-0002-8770-2464; Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195, N02-HL-6-4278, N01-HC-95159, 95169, RR-024156, R01-HL-071739, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, N01-HC-65226]; Affymetrix for genotyping services; National Institute on Aging [N01-AG-12100]; National Eye Institute; National Institute on Deafness and Other Communication Disorders; National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (Icelandic parliament); MESA; MESA Family; MESA CARe; MESA SHARe project; Heinz Nixdorf Recall Study; Heinz Nixdorf Foundation; German Foundation of Research (DFG); Malmo Diet and Cancer study; Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation; Malmo city council; Copenhagen City Heart Study; Danish Heart Foundation FX The Framingham Heart Study was supported by a grant (N01-HC-25195) from the National Heart, Lung, and Blood Institute (NHLBI) and an NHLBI contract (N02-HL-6-4278) with Affymetrix for genotyping services; the Age, Gene/Environment Susceptibility-Reykjavik Study, by a grant from the National Institute on Aging (N01-AG-12100) and by the National Eye Institute, the National Institute on Deafness and Other Communication Disorders, the NHLBI, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (Icelandic parliament); the MESA, MESA Family, MESA CARe, and the MESA SHARe project, by grants (N01-HC-95159 through 95169, RR-024156, R01-HL-071739, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, N02-HL-6-4278, and N01-HC-65226) from the NHLBI; the Heinz Nixdorf Recall Study, by the Heinz Nixdorf Foundation and the German Foundation of Research (DFG); the Malmo Diet and Cancer study, by the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the Malmo city council; and the Copenhagen City Heart Study, by the Danish Heart Foundation. Detailed information on support for individual authors and analyses is available in the Supplementary Appendix. NR 47 TC 164 Z9 170 U1 2 U2 30 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 7 PY 2013 VL 368 IS 6 BP 503 EP 512 DI 10.1056/NEJMoa1109034 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 083VU UT WOS:000314494100001 PM 23388002 ER PT J AU Tsiamas, P Liu, B Cifter, F Ngwa, WF Berbeco, RI Kappas, C Theodorou, K Marcus, K Makrigiorgos, MG Sajo, E Zygmanski, P AF Tsiamas, Panagiotis Liu, Bo Cifter, Fulya Ngwa, Wilfred F. Berbeco, Ross I. Kappas, Constantin Theodorou, Kiriaki Marcus, Karen Makrigiorgos, Mike G. Sajo, Erno Zygmanski, Piotr TI Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO-SIMULATION; RADIATION-THERAPY; X-RAYS; ENERGY; BRACHYTHERAPY; ELECTRONS; RADIOSENSITIZATION; DNA AB This study determines the optimal clinical scenarios for gold nanoparticle dose enhancement as a function of irradiation conditions and potential biological targets using megavoltage x-ray beams. Four hundred and eighty clinical beams were studied for different potential cellular or sub-cellular targets. Beam quality was determined based on a 6 MV linac with and without a flattening filter for various delivery conditions. Dose enhancement ratios DER = D-GNP/D-water were calculated for all cases using the GEANT4 Monte Carlo code and the CEPXS/ONEDANT radiation transport deterministic code. Dose enhancement using GEANT4 agreed with CEPXS/ONEDANT. DER for unflattened beams is similar to 2 times larger than for flattened beams. The maximum DER values were calculated for split-IMRT fields (similar to 6) and for out-of-field areas of an unflattened linac (similar to 17). In-field DER values, at the surface of gold nanoparticles, ranged from 2.2 to 4.2 (flattened beam) and from 3 to 4.7 (unflattened beams). For a GNP cluster with thicknesses of 10 and 100 nm, the DER ranges from 14% to 287%. DER is the greatest for split-IMRT, larger depths, out-of-field areas and/or unflattened linac. Mapping of a GNP location in tumor and normal tissue is essential for efficient and safe delivery of nanoparticle-enhanced radiotherapy. C1 [Tsiamas, Panagiotis; Liu, Bo; Ngwa, Wilfred F.; Berbeco, Ross I.; Marcus, Karen; Makrigiorgos, Mike G.; Zygmanski, Piotr] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Tsiamas, Panagiotis; Liu, Bo; Ngwa, Wilfred F.; Berbeco, Ross I.; Marcus, Karen; Makrigiorgos, Mike G.; Zygmanski, Piotr] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Tsiamas, Panagiotis; Kappas, Constantin; Theodorou, Kiriaki] Univ Thessaly, Sch Med, Dept Med Phys, Larisa 4100, Greece. [Liu, Bo] Heidelberg Univ, Med Fac Mannheim, D-68167 Mannheim, Germany. [Cifter, Fulya; Sajo, Erno] Univ Massachusetts Lowell, Dept Phys & Appl Phys, Lowell, MA 01854 USA. RP Sajo, E (reprint author), Univ Massachusetts Lowell, Dept Phys & Appl Phys, Lowell, MA 01854 USA. EM erno_sajo@uml.edu; pzygmanski@lroc.harvard.edu NR 28 TC 27 Z9 27 U1 1 U2 38 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 7 PY 2013 VL 58 IS 3 BP 451 EP 464 DI 10.1088/0031-9155/58/3/451 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 071CV UT WOS:000313564200006 PM 23302438 ER PT J AU Salari, E Unkelbach, J AF Salari, Ehsan Unkelbach, Jan TI A column-generation-based method for multi-criteria direct aperture optimization SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; FLUENCE MAP OPTIMIZATION; RADIATION-THERAPY; PARETO SURFACES; IMRT; ALGORITHMS AB Navigation-based multi-criteria optimization has been introduced to radiotherapy planning in order to allow the interactive exploration of trade-offs between conflicting clinical goals. However, this has been mainly applied to fluence map optimization. The subsequent leaf sequencing step may cause dose discrepancy, leading to human iteration loops in the treatment planning process that multi-criteria methods were meant to avoid. To circumvent this issue, this paper investigates the application of direct aperture optimization methods in the context of multi-criteria optimization. We develop a solution method to directly obtain a collection of apertures that can adequately span the entire Pareto surface. To that end, we extend the column generation method for direct aperture optimization to a multi-criteria setting in which apertures that can improve the entire Pareto surface are sequentially identified and added to the treatment plan. Our proposed solution method can be embedded in a navigation-based multi-criteria optimization framework, in which the treatment planner explores the trade-off between treatment objectives directly in the space of deliverable apertures. Our solution method is demonstrated for a paraspinal case where the trade-off between target coverage and spinal-cord sparing is studied. The computational results validate that our proposed method obtains a balanced approximation of the Pareto surface over a wide range of clinically relevant plans. C1 [Salari, Ehsan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Salari, E (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM salari.ehsan@mgh.harvard.edu FU National Cancer Institute [R01 CA118200-01] FX The project described was supported by Award No R01 CA118200-01 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors would like to thank David Craft for providing feedback on the manuscript. NR 30 TC 7 Z9 7 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 7 PY 2013 VL 58 IS 3 BP 621 EP 639 DI 10.1088/0031-9155/58/3/621 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 071CV UT WOS:000313564200016 PM 23318527 ER PT J AU Dhabangi, A Mworozi, E Lubega, IR Cserti-Gazdewich, CM Maganda, A Dzik, WH AF Dhabangi, Aggrey Mworozi, Edison Lubega, Irene R. Cserti-Gazdewich, Christine M. Maganda, Albert Dzik, Walter H. TI The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial SO MALARIA JOURNAL LA English DT Article DE Severe malarial anaemia; Lactic acidosis; Blood storage age; Blood transfusion; Children ID AFRICAN CHILDREN; CELLS AB Background: Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. Methods: Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin <= 5 g/dL) and lactic acidosis (blood lactate >= 5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. Results: Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to lactic acidosis resolution was 2.65 hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60-4.10) in the long storage arm (p value = 0.264). Conclusion: Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. C1 [Dhabangi, Aggrey] Makerere Univ, Child Hlth & Dev Ctr, Kampala, Uganda. [Mworozi, Edison; Lubega, Irene R.] Minist Hlth Kampala, Mulago Hosp, Dept Paediat & Child Hlth, Kampala, Uganda. [Cserti-Gazdewich, Christine M.] Univ Toronto, Dept Hematol, Toronto, ON, Canada. [Maganda, Albert] Baylor Coll Med Childrens Fdn, Kampala, Uganda. [Dzik, Walter H.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dhabangi, A (reprint author), Makerere Univ, Child Hlth & Dev Ctr, Kampala, Uganda. EM adhabangi@gmail.com FU Belgian Technical Co-operation (BTC); Carnegie next generation of academics project FX This research was supported in part by scholarship grants from the Belgian Technical Co-operation (BTC) and the Carnegie next generation of academics project 2010 - 2012. The Cytoadherence in Paediatric Malaria (CPM) project provided kind donations of all the study equipment used. The authors wish to thank the research assistants (Josephine Badaru and Victor Tumukunde), the laboratory technicians of ACU (Edson Sabuni, Rehema Namwanje, Timothy Pande and Josephine Birungi), Dr Dorothy Kyeyune, Director of the Uganda National Blood Transfusion Service, all the paediatricians (particularly Dr Ezekiel Mupere, Dr Eric Wobudeya and Prof Heather A Hume) in the Department of Paediatrics and Child Health at Makerere University for all their respective support. We thank the caretakers and the children who participated in this study. We do appreciate Uganda Society for Health Scientists (USHS) for the manuscript-writing workshop. NR 14 TC 9 Z9 9 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD FEB 6 PY 2013 VL 12 AR 55 DI 10.1186/1475-2875-12-55 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 118ZI UT WOS:000317065700001 PM 23388470 ER PT J AU Mueller, S Wang, DH Fox, MD Yeo, BTT Sepulcre, J Sabuncu, MR Shafee, R Lu, J Liu, HS AF Mueller, Sophia Wang, Danhong Fox, Michael D. Yeo, B. T. Thomas Sepulcre, Jorge Sabuncu, Mert R. Shafee, Rebecca Lu, Jie Liu, Hesheng TI Individual Variability in Functional Connectivity Architecture of the Human Brain SO NEURON LA English DT Article ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; INTERSUBJECT VARIABILITY; PREFRONTAL CORTEX; GENETIC INFLUENCES; EVOLUTION; NETWORKS; SYSTEM; CYTOARCHITECTURE; MORPHOMETRY AB The fact that people think or behave differently from one another is rooted in individual differences in brain anatomy and connectivity. Here, we used repeated-measurement resting-state functional MRI to explore intersubject variability in connectivity. Individual differences in functional connectivity were heterogeneous across the cortex, with significantly higher variability in heteromodal association cortex and lower variability in unimodal cortices. Intersubject variability in connectivity was significantly correlated with the degree of evolutionary cortical expansion, suggesting a potential evolutionary root of functional variability. The connectivity variability was also related to variability in sulcal depth but not cortical thickness, positively correlated with the degree of long-range connectivity but negatively correlated with local connectivity. A meta-analysis further revealed that regions predicting individual differences in cognitive domains are predominantly located in regions of high connectivity variability. Our findings have potential implications for understanding brain evolution and development, guiding intervention, and interpreting statistical maps in neuroimaging. C1 [Mueller, Sophia; Wang, Danhong; Yeo, B. T. Thomas; Sepulcre, Jorge; Sabuncu, Mert R.; Liu, Hesheng] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mueller, Sophia; Sepulcre, Jorge; Shafee, Rebecca] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany. [Fox, Michael D.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yeo, B. T. Thomas] Duke NUS Grad Med Sch, Neurosci & Behav Disorders Program, Singapore 169857, Singapore. [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lu, Jie] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China. RP Lu, J (reprint author), Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China. EM jielu@nmr.mgh.harvard.edu; hesheng@nmr.mgh.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509; Yeo, B.T. Thomas/0000-0002-0119-3276 FU NINDS [K25NS069805]; NARSAD; German Research Foundation [MU 3222/2-1] FX This work was supported by NINDS grant K25NS069805, NARSAD Young Investigator Grant, and a research grant from the German Research Foundation (MU 3222/2-1). The authors would like to thank Drs. Randy L. Buckner and Bruce Fischl for discussions and comments on the manuscript. NR 64 TC 124 Z9 128 U1 7 U2 52 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB 6 PY 2013 VL 77 IS 3 BP 586 EP 595 DI 10.1016/j.neuron.2012.12.028 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 118MY UT WOS:000317030800018 PM 23395382 ER PT J AU Zeliadt, SB Hannon, PA Trivedi, RB Bonner, LM Vu, TT Simons, C Kimmie, CA Hu, EY Zipperer, C Lin, DW AF Zeliadt, Steven B. Hannon, Peggy A. Trivedi, Ranak B. Bonner, Laura M. Vu, Thuy T. Simons, Carol Kimmie, Crystal A. Hu, Elaine Y. Zipperer, Chris Lin, Daniel W. TI A preliminary exploration of the feasibility of offering men information about potential prostate cancer treatment options before they know their biopsy results SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Prostate cancer; Biopsy; Decision aid; Prostate biopsy; Treatment decision making ID DECISION-MAKING; AIDS AB Background: A small pre-test study was conducted to ascertain potential harm and anxiety associated with distributing information about possible cancer treatment options at the time of biopsy, prior to knowledge about a definitive cancer diagnosis. Priming men about the availability of multiple options before they have a confirmed diagnosis may be an opportunity to engage patients in more informed decision-making. Methods: Men with an elevated PSA test or suspicious Digital Rectal Examination (DRE) who were referred to a urology clinic for a biopsy were randomized to receive either the clinic's usual care (UC) biopsy instruction sheet (n = 11) or a pre-biopsy educational (ED) packet containing the biopsy instruction sheet along with a booklet about the biopsy procedure and a prostate cancer treatment decision aid originally written for newly diagnosed men that described in detail possible treatment options (n = 18). Results: A total of 62% of men who were approached agreed to be randomized, and 83% of the ED group confirmed they used the materials. Anxiety scores were similar for both groups while awaiting the biopsy procedure, with anxiety scores trending lower in the ED group: 41.2 on a prostate-specific anxiety instrument compared to 51.7 in the UC group (p = 0.13). ED participants reported better overall quality of life while awaiting biopsy compared to the UC group (76.4 vs. 48.5, p = 0.01). The small number of men in the ED group who went on to be diagnosed with cancer reported being better informed about the risks and side effects of each option compared to men diagnosed with cancer in the UC group (p = 0.07). In qualitative discussions, men generally reported they found the pre-biopsy materials to be helpful and indicated having information about possible treatment options reduced their anxiety. However, 2 of 18 men reported they did not want to think about treatment options until after they knew their biopsy results. Conclusions: In this small sample offering pre-biopsy education about potential treatment options was generally well received by patients, appeared to be beneficial to men who went on to be diagnosed, and did not appear to increase anxiety unnecessarily among those who had a negative biopsy. C1 [Zeliadt, Steven B.; Trivedi, Ranak B.; Bonner, Laura M.; Simons, Carol; Hu, Elaine Y.] VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zeliadt, Steven B.; Hannon, Peggy A.; Trivedi, Ranak B.; Vu, Thuy T.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Kimmie, Crystal A.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Zipperer, Chris] Washington State Dept Hlth, Canc Prevent & Control Unit, Olympia, WA USA. [Kimmie, Crystal A.; Lin, Daniel W.] Dept Vet Affairs Med Ctr, Urol Serv, Seattle, WA USA. [Lin, Daniel W.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. RP Zeliadt, SB (reprint author), VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Metropolitan Pk West,1100 Olive Way 1400, Seattle, WA 98101 USA. EM szeliadt@uw.edu FU Washington State Department of Health [N17493]; Centers for Disease Control and Prevention; National Cancer Institute through the Cancer Prevention and Control Research Network [1-U48-DP-000050]; Department of Veterans Affairs [HFP 83-027] FX This work was conducted at the VA Puget Sound Healthcare System. Financial support for this study was provided in part by a contract with the Washington State Department of Health (Contract Number N17493; CK), the Centers for Disease Control and Prevention and the National Cancer Institute through the Cancer Prevention and Control Research Network (Grant 1-U48-DP-000050; PAH; TV), and by the Department of Veterans Affairs (HFP 83-027; SBZ). The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or of the United States government. NR 29 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD FEB 6 PY 2013 VL 13 AR 19 DI 10.1186/1472-6947-13-19 PG 9 WC Medical Informatics SC Medical Informatics GA 107NL UT WOS:000316224400001 PM 23388205 ER PT J AU Jeon, JY Jeong, DH Park, MG Lee, JW Chu, SH Park, JH Lee, MK Sato, K Ligibel, JA Meyerhardt, JA Kim, NK AF Jeon, Justin Y. Jeong, Duck Hyoun Park, Min Geun Lee, Ji-Won Chu, Sang Hui Park, Ji-Hye Lee, Mi Kyung Sato, Kaori Ligibel, Jennifer A. Meyerhardt, Jeffrey A. Kim, Nam Kyu TI Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer SO PLOS ONE LA English DT Article ID BODY-MASS INDEX; INDEPENDENT RISK-FACTOR; IGF-BINDING-PROTEINS; IOWA WOMENS HEALTH; SERUM C-PEPTIDE; MELLITUS; INSULIN; TYPE-2; METAANALYSIS; MORTALITY AB Background: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum). Patients and methods: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. Results: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11-1.92), DFS (HR: 1.45, 95% CI: 1.15-1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98-1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007). Conclusions: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer. C1 [Jeong, Duck Hyoun; Park, Min Geun; Kim, Nam Kyu] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea. [Jeon, Justin Y.; Sato, Kaori; Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jeon, Justin Y.; Park, Ji-Hye; Lee, Mi Kyung] Yonsei Univ, Sports Med Lab, Seoul 120749, South Korea. [Lee, Ji-Won] Yonsei Univ, Coll Med, Dept Family Med, Seoul, South Korea. [Chu, Sang Hui] Yonsei Univ, Coll Nursing, Biobehav Res Ctr, Dept Clin Nursing Sci, Seoul 120749, South Korea. [Chu, Sang Hui] Yonsei Univ, Coll Nursing, Biobehav Res Ctr, Nursing Policy & Res Inst, Seoul 120749, South Korea. RP Meyerhardt, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org; namkyuk@yuhs.ac OI Kim, Nam-Kyu/0000-0003-0639-5632 FU NCI NIH HHS [R01 CA149222] NR 51 TC 14 Z9 14 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 6 PY 2013 VL 8 IS 2 AR e55196 DI 10.1371/journal.pone.0055196 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092WJ UT WOS:000315153400068 PM 23405123 ER PT J AU Liu, Y Yang, XS Guo, CY Nie, P Liu, Y Ma, J AF Liu, Yong Yang, Xuesen Guo, Chenying Nie, Pan Liu, Yan Ma, Jie TI Essential Role of MFG-E8 for Phagocytic Properties of Microglial Cells SO PLOS ONE LA English DT Article ID GLOBULE-EGF FACTOR-8; SYSTEMIC-LUPUS-ERYTHEMATOSUS; APOPTOTIC CELLS; NEURONAL DEATH; MACROPHAGE CLEARANCE; LENTIVIRUS VECTOR; VIABLE NEURONS; PHOSPHATIDYLSERINE; DISEASE; IDENTIFICATION AB Milk fat globule factor-E8 (MFG-E8) has been regarded as a key factor involved in the phagocytosis of apoptotic cells. We induced a lentivirus into the microglial cells for the augmentation or abrogation of MFG-E8 expression in mouse microglial cells, and investigated phagocytosis of phosphatidylserine tagged human red blood cells (hRBCs) in co-cultures. Increased MFG-E8 levels were associated with a significant increase in phagocytic activity compared to the controls. Conversely, phagocytosis dramitically decreased due to the abrogation of MFG-E8. In addition, the expression of the inflammatory cytokines, TNF-alpha and IL-1 beta, also increased or decreased in the microglial cells with the augmentation or abrogation of MFG-E8, respectively. Our findings indicate that the enhanced expression of MFG-E8 could increase phagocytosis of apoptotic cells; conversely, the rate of phagocytosis and the expression of inflammatory cytokines decreased when MFG-E8 expression was knocked down. Our results confirm that MFG-E8 plays an important role in phagocytosis, and possibly serves as an essential signal molecule for microglial cells. C1 [Liu, Yong] Third Mil Med Univ, SW Eye Hosp, Southwest Hosp, Chongqing, Peoples R China. [Yang, Xuesen] Third Mil Med Univ, Inst Trop Med, Chongqing, Peoples R China. [Guo, Chenying; Ma, Jie] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol,Med Sch, Boston, MA USA. [Nie, Pan; Liu, Yan] Southwest Univ, Coll Life Sci, Chongqing, Peoples R China. RP Liu, Y (reprint author), Third Mil Med Univ, SW Eye Hosp, Southwest Hosp, Chongqing, Peoples R China. EM liu_yong2012@yahoo.com FU National Natural Science Foundation of China [30700931, 30970672] FX This study was supported by the National Natural Science Foundation of China (No. 30700931 to Yong Liu and No. 30970672 to Xuesen Yang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 8 Z9 9 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 6 PY 2013 VL 8 IS 2 AR e55754 DI 10.1371/journal.pone.0055754 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092WJ UT WOS:000315153400154 PM 23405209 ER PT J AU Gallagher, TQ Brigger, MT Hartnick, CJ AF Gallagher, Thomas Q. Brigger, Matthew T. Hartnick, Christopher J. TI Bleeding Risk and Dexamethasone Use in Children Undergoing Tonsillectomy Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Gallagher, Thomas Q.] USN, Med Ctr Portsmouth, Dept Otolaryngol, Portsmouth, VA USA. [Brigger, Matthew T.] USN, San Diego Med Ctr, Dept Otolaryngol, San Diego, CA 92152 USA. [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA. RP Gallagher, TQ (reprint author), USN, Med Ctr Portsmouth, Dept Otolaryngol, Portsmouth, VA USA. EM christopher_hartnick@meei.harvard.edu NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2013 VL 309 IS 5 BP 437 EP 438 DI 10.1001/jama.2012.113521 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 083LY UT WOS:000314466900012 PM 23385257 ER PT J AU Bangalore, S Steg, PG Bhatt, DL AF Bangalore, Sripal Steg, P. Gabriel Bhatt, Deepak L. TI beta-Blocker Use for Patients With or at Risk for Coronary Artery Disease Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID MYOCARDIAL-INFARCTION; ATENOLOL C1 [Bangalore, Sripal] NYU, Sch Med, New York, NY USA. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bangalore, S (reprint author), NYU, Sch Med, New York, NY USA. EM sripalbangalore@gmail.com RI Bangalore, Sripal/B-6246-2013; OI Bangalore, Sripal/0000-0001-9485-0652 NR 6 TC 1 Z9 1 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2013 VL 309 IS 5 BP 439 EP 440 DI 10.1001/jama.2012.128872 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 083LY UT WOS:000314466900016 PM 23385261 ER PT J AU Axelrod, L Shah, DJ Jena, AB AF Axelrod, Lloyd Shah, Deep J. Jena, Anupam B. TI The European Working Time Directive An Uncontrolled Experiment in Medical Care and Education SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Axelrod, Lloyd; Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Axelrod, Lloyd] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. [Shah, Deep J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jena, Anupam B.] Hlth Care Policy, Boston, MA USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Axelrod, L (reprint author), Massachusetts Gen Hosp, Dept Med, Div Endocrine, Boston, MA 02114 USA. EM laxelrod@partners.org NR 8 TC 15 Z9 15 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2013 VL 309 IS 5 BP 447 EP 448 DI 10.1001/jama.2012.148065 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 083LY UT WOS:000314466900023 PM 23385268 ER PT J AU Inouye, SK O'Connell, JJ Puelle, MR AF Inouye, Sharon K. O'Connell, James J. Puelle, Margaret R. TI Falling Off the Edge SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HOMELESS ADULTS; MENTAL-ILLNESS C1 [Inouye, Sharon K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA 02138 USA. [O'Connell, James J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02138 USA. [Inouye, Sharon K.; O'Connell, James J.] Boston Healthcare Homeless Program, Boston, MA USA. RP Inouye, SK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA 02138 USA. EM agingbraincenter@hsl.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2013 VL 309 IS 5 BP 451 EP 452 DI 10.1001/jama.2012.214089 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 083LY UT WOS:000314466900025 PM 23385270 ER PT J AU Sano, M AF Sano, Mary TI Never Too Fit for Body and Mind SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PHYSICAL-ACTIVITY; CARDIORESPIRATORY FITNESS; MORTALITY; MEN; IMPAIRMENT; EXERCISE; ADULTS; WOMEN; RISK C1 [Sano, Mary] Mt Sinai Sch Med, New York, NY USA. [Sano, Mary] James J Peters Vet Affairs Med Ctr, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Bronx, NY USA. [Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Sano, M (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM mary.sano@mssm.edu FU NIA NIH HHS [P50 AG005138] NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 5 PY 2013 VL 158 IS 3 BP 213 EP 214 DI 10.7326/0003-4819-158-3-201302050-00013 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 087JP UT WOS:000314757900010 PM 23381042 ER PT J AU Rueda, BR Davis, JS AF Rueda, Bo R. Davis, John S. TI No REST for fibroids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID UTERINE LEIOMYOMA; PATHWAY; MYOMETRIUM C1 [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Davis, John S.] VA Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68105 USA. [Davis, John S.] Univ Nebraska Med Ctr, Olson Ctr Womens Hlth, Dept Obstet & Gynecol, Omaha, NE 68198 USA. RP Davis, JS (reprint author), VA Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68105 USA. EM jsdavis@unmc.edu NR 18 TC 0 Z9 0 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 1980 EP 1981 DI 10.1073/pnas.1222730110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800016 PM 23355686 ER PT J AU Tomasetti, C Vogelstein, B Parmigiani, G AF Tomasetti, Cristian Vogelstein, Bert Parmigiani, Giovanni TI Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer evolution; mathematical modeling; stochastic processes; driver mutation; passenger mutation ID STEM-CELLS; EVOLUTION; PROGRESSION; GENES; LANDSCAPE; LEUKEMIA; GENOME; TIME AB Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this topic. To gain insights into this fundamental issue, we formulated a mathematical model for the evolution of somatic mutations in which all relevant phases of a tissue's history are considered. The model makes the prediction, validated by our empirical findings, that the number of somatic mutations in tumors of self-renewing tissues is positively correlated with the age of the patient at diagnosis. Importantly, our analysis indicates that half or more of the somatic mutations in certain tumors of self-renewing tissues occur before the onset of neoplasia. The model also provides a unique way to estimate the in vivo tissue-specific somatic mutation rates in normal tissues directly from the sequencing data of tumors. Our results have substantial implications for the interpretation of the large number of genome-wide cancer studies now being undertaken. C1 [Tomasetti, Cristian; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tomasetti, Cristian; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. RP Tomasetti, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM cristian@jimmy.harvard.edu; bertvog@gmail.com; gp@jimmy.harvard.edu OI Tomasetti, Cristian/0000-0003-3277-4804 FU National Institutes of Health (NIH) [T32 CA009337]; NIH/National Cancer Institute [5P30 CA006516-46] FX C.T. was supported in part by the National Institutes of Health (NIH) under Grant T32 CA009337. G. P. was supported in part by the NIH/National Cancer Institute Grant 5P30 CA006516-46. NR 26 TC 110 Z9 113 U1 1 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 1999 EP 2004 DI 10.1073/pnas.1221068110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800019 PM 23345422 ER PT J AU Liu, SZ Ho, CK Ouyang, J Zou, L AF Liu, Shizhou Ho, Chu Kwen Ouyang, Jian Zou, Lee TI Nek1 kinase associates with ATR-ATRIP and primes ATR for efficient DNA damage signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID REPLICATION CHECKPOINT RESPONSE; CELL-CYCLE ARREST; 2-DEPENDENT PHOSPHORYLATION; G2/M CHECKPOINT; CHK1 ACTIVATION; PROTEIN-KINASE; KIDNEY FAILURE; CLASPIN; MUTATIONS; DEGRADATION AB The master checkpoint kinase ATR (ATM and Rad3-related) and its partner ATRIP (ATR-interacting protein) exist as a complex and function together in the DNA damage response. Unexpectedly, we found that the stability of the ATR-ATRIP complex is regulated by an unknown kinase independently of DNA damage. In search for this regulator of ATR-ATRIP, we found that a single member of the NIMA (never in mitosis A)-related kinase family, Nek1, is critical for initiating the ATR response. Upon DNA damage, cells lacking Nek1 failed to efficiently phosphorylate multiple ATR substrates and support ATR autophosphorylation at threnine 1989, one of the earliest events during the ATR response. The ability of Nek1 to promote ATR activation relies on the kinase activity of Nek1 and its interaction with ATR-ATRIP. Importantly, even in undamaged cells, Nek1 is required for maintaining the levels of ATRIP, the association between ATR and ATRIP, and the basal kinase activity of ATR. Thus, as an ATR-associated kinase, Nek1, enhances the stability and activity of ATR-ATRIP before DNA damage, priming ATR-ATRIP for a robust DNA damage response. C1 [Liu, Shizhou; Ho, Chu Kwen; Ouyang, Jian; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zou, Lee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Shizhou] China Med Univ, Affiliated Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China. RP Liu, SZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM Liu_shizhou@hotmail.com; zou.lee@mgh.harvard.edu FU National Institutes of Health [GM076388]; Federal Share of Proton Income FX We thank members of the Zou laboratory for helpful discussions. This work was supported by the National Institutes of Health Grant GM076388 and a grant funded by the Federal Share of Proton Income (to L.Z.). L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar. NR 46 TC 14 Z9 14 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2175 EP 2180 DI 10.1073/pnas.1217781110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800049 PM 23345434 ER PT J AU Yan, D Zhu, Y Walsh, T Xie, DH Yuan, HJ Sirmaci, A Fujikawa, T Wong, ACY Loh, TL Du, LL Grati, M Vlajkovic, SM Blanton, S Ryan, AF Chen, ZY Thorne, PR Kachar, B Tekin, M Zhao, HB Housley, GD King, MC Liu, XZ AF Yan, Denise Zhu, Yan Walsh, Tom Xie, Dinghua Yuan, Huijun Sirmaci, Asli Fujikawa, Taro Wong, Ann Chi Yan Loh, Tze L. Du, Lilin Grati, M'hamed Vlajkovic, Srdjan M. Blanton, Susan Ryan, Allen F. Chen, Zheng-Yi Thorne, Peter R. Kachar, Bechara Tekin, Mustafa Zhao, Hong-Bo Housley, Gary D. King, Mary-Claire Liu, Xue Z. TI Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE channel; deafness; genomics; presbycusis ID ION CHANNELS; AUDITORY NEUROTRANSMISSION; SOUND TRANSDUCTION; COCHLEAR FUNCTION; RAT COCHLEA; SUBUNIT; MOUSE; LOCALIZATION; STEREOCILIA; EXPRESSION AB Age-related hearing loss and noise-induced hearing loss are major causes of human morbidity. Here we used genetics and functional studies to showthat a shared cause of these disordersmay be loss of function of the ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) that is expressed in sensory and supporting cells of the cochlea. Genomic analysis of dominantly inherited, progressive sensorineural hearing loss DFNA41 in a six-generation kindred revealed a rare heterozygous allele, P2RX2 c.178G > T (p.V60L), at chr12: 133,196,029, which cosegregated with fully penetrant hearing loss in the index family, and also appeared in a second family with the same phenotype. The mutation was absent from more than 7,000 controls. P2RX2 p.V60L abolishes two hallmark features of P2X(2) receptors: ATP-evoked inward current response and ATP-stimulated macropore permeability, measured as loss of ATP-activated FM1-43 fluorescence labeling. Coexpression of mutant and WT P2X(2) receptor subunits significantly reduced ATP-activated membrane permeability. P2RX2-null mice developed severe progressive hearing loss, and their early exposure to continuous moderate noise led to high-frequency hearing loss as young adults. Similarly, among family members heterozygous for P2RX2 p.V60L, noise exposure exacerbated high-frequency hearing loss in young adulthood. Our results suggest that P2X(2) function is required for life-long normal hearing and for protection from exposure to noise. C1 [Yan, Denise; Du, Lilin; Grati, M'hamed; Liu, Xue Z.] Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL 33136 USA. [Zhu, Yan; Zhao, Hong-Bo] Univ Kentucky, Med Ctr, Dept Otolaryngol, Lexington, KY 40536 USA. [Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Xie, Dinghua; Liu, Xue Z.] Cent S Univ, Dept Otolaryngol Head & Neck Surg, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. [Yuan, Huijun] Chinese Peoples Liberat Army Gen Hosp, Inst Otolaryngol, Beijing 100853, Peoples R China. [Sirmaci, Asli; Blanton, Susan; Tekin, Mustafa; Liu, Xue Z.] Univ Miami, Sch Med, Dept Human Genet, Miami, FL 33136 USA. [Fujikawa, Taro; Grati, M'hamed; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. [Wong, Ann Chi Yan; Loh, Tze L.; Housley, Gary D.] Univ New S Wales, Sch Med Sci, Translat Neurosci Facil, Sydney, NSW 2052, Australia. [Wong, Ann Chi Yan; Loh, Tze L.; Housley, Gary D.] Univ New S Wales, Sch Med Sci, Dept Physiol, Sydney, NSW 2052, Australia. [Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Med Sci, Dept Physiol, Auckland 1, New Zealand. [Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Med Sci, Ctr Brain Res, Auckland 1, New Zealand. [Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Populat Hlth, Sect Audiol, Auckland 1, New Zealand. [Ryan, Allen F.] Univ Calif San Diego, Dept Otolaryngol, La Jolla, CA 92093 USA. [Ryan, Allen F.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Chen, Zheng-Yi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab,Dept Otol & Laryngol, Boston, MA 02114 USA. RP King, MC (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM mcking@u.washington.edu; xliu@med.miami.edu OI Walsh, Tom/0000-0002-8875-0310; Wong, Ann CY/0000-0001-7011-0369; Housley, Gary/0000-0002-8413-588X; Vlajkovic, Srdjan/0000-0001-8548-6844 FU National Institutes of Health, National Institute on Deafness and Other Communication Disorders [R01 DC012546, R01 DC005575, R01 DC005989, R01 HL105631, R01 DC009645, R01 DC000139, R01 DC005641]; Veterans' Administration; Australia National Health and Medical Research Council [630618]; New Zealand Marsden Fund; Health Research Council and Deafness Research Foundation; People's Republic of China National Natural Science Foundation [30528025] FX We thank the families for their participation in the study. We thank Menwei Cai, Pu Dai, Dongyi Han, Kaisun Li, Chunyu Liang, Zian Xiao, and Shiming Yang for contributions to the fieldwork in China; Anne Thornton, Ming Lee, Xiaomai Ouyang, and Suleyman Gulsuner for contributions to genomics and bioinformatics; Kwang Pak, Eduardo Chavez, Jeremy Pinyon, Rachel Morton-Jones, Sherif Tadros, and Yogeesan Sivakumaran for contributions to the mouse experiments; Debra Cockayne for supporting the establishment of the mouse model; Edward Crawford for designing and engineering the environmental chambers; and Karen B. Avraham, Walter Nance, Yanbin Zhang, and Jianxin Bao for helpful discussions. This work was supported by the National Institutes of Health, National Institute on Deafness and Other Communication Disorders [Grants R01 DC012546 (to X.Z.L.), R01 DC005575 (to X.Z.L.), R01 DC005989 (to H.-B.Z.), R01 HL105631 (to Y.Z.), R01 DC009645 (to M. T.), R01 DC000139 (to A. F. R.), and R01 DC005641 (to M.-C. K. and T. W.), and the intramural program (B. K.)], the Veterans' Administration (A. F. R.), the Australia National Health and Medical Research Council [Grant 630618 (to G. D. H. and A. F. R.)], the New Zealand Marsden Fund (G. D. H.) and Health Research Council and Deafness Research Foundation (P. R. T., G. D. H., and S. M. V.), and the People's Republic of China National Natural Science Foundation [Grant 30528025 (to X.Z.L.)]. NR 40 TC 31 Z9 36 U1 3 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2228 EP 2233 DI 10.1073/pnas.1222285110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800058 PM 23345450 ER PT J AU Oksenych, V Kumar, V Liu, XY Guo, CG Schwer, B Zha, S Alt, FW AF Oksenych, Valentyn Kumar, Vipul Liu, Xiangyu Guo, Chunguang Schwer, Bjoern Zha, Shan Alt, Frederick W. TI Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cernunnos; nej1; nhej1; SCID; T-FISH ID CLASS SWITCH RECOMBINATION; DEPENDENT PROTEIN-KINASE; LEAKY SCID PHENOTYPE; DOUBLE-STRAND BREAKS; SIGNAL JOINT; LYMPHOCYTE DEVELOPMENT; CATALYTIC SUBUNIT; B-CELLS; ATM; TRANSLOCATIONS AB Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway that is required for assembly of antigen receptor variable region gene segments by V(D)J recombination. Recombination activating gene endonuclease initiates V(D)J recombination by generating DSBs between two V (D) J coding gene segments and flanking recombination signal sequences (RS), with the two coding ends and two RS ends joined by C-NHEJ to form coding joins and signal joins, respectively. During C-NHEJ, recombination activating gene factor generates two coding ends as covalently sealed hairpins and RS ends as blunt 5'-phosphorylated DSBs. Opening and processing of coding end hairpins before joining by C-NHEJ requires the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). However, C-NHEJ of RS ends, which do not require processing, occurs relatively normally in the absence of DNA-PKcs. The XRCC4-like factor (XLF) is a C-NHEJ component that is not required for C-NHEJ of chromosomal signal joins or coding joins because of functional redundancy with ataxia telangiectasia mutated kinase, a protein that also has some functional overlap with DNA-PKcs in this process. Here, we show that XLF has dramatic functional redundancy with DNA-PKcs in the V(D)J SJ joining process, which is nearly abrogated in their combined absence. Moreover, we show that XLF functionally overlaps with DNA-PKcs in normal mouse development, promotion of genomic stability in mouse fibroblasts, and in IgH class switch recombination in mature B cells. Our findings suggest that DNA-PKcs has fundamental roles in C-NHEJ processes beyond end processing that have been masked by functional overlaps with XLF. C1 [Oksenych, Valentyn; Kumar, Vipul; Guo, Chunguang; Schwer, Bjoern; Alt, Frederick W.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Oksenych, Valentyn; Kumar, Vipul; Guo, Chunguang; Schwer, Bjoern; Alt, Frederick W.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Oksenych, Valentyn; Kumar, Vipul; Guo, Chunguang; Schwer, Bjoern; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Liu, Xiangyu; Zha, Shan] Columbia Univ, Coll Phys & Surg, Inst Canc Genet, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Liu, Xiangyu; Zha, Shan] Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. RP Alt, FW (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu RI liu, xiangyu/D-8213-2014; OI Oksenych, Valentyn/0000-0002-5088-3791 FU National Institutes of Health (NIH) [AI076210]; NIH/National Cancer Institute Grant [NCI 5R01CA158073]; National Institute of Aging/NIH [K01 AG043630] FX This work is supported by National Institutes of Health (NIH) Grant AI076210 (to F. W. A.) and NIH/National Cancer Institute Grant NCI 5R01CA158073 (to S.Z). B. S. is supported by the National Institute of Aging/NIH under Award K01 AG043630. F. W. A. is an investigator of the Howard Hughes Medical Institute. C.G. is a fellow of Cancer Research Institute. NR 44 TC 14 Z9 17 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2234 EP 2239 DI 10.1073/pnas.1222573110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800059 PM 23345432 ER PT J AU Chang, J Burkett, PR Borges, CM Kuchroo, VK Turka, LA Chang, CH AF Chang, JiHoon Burkett, Patrick R. Borges, Christopher M. Kuchroo, Vijay K. Turka, Laurence A. Chang, Cheong-Hee TI MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROR-GAMMA-T; TGF-BETA; AUTOIMMUNE INFLAMMATION; TOXOPLASMA-GONDII; DIFFERENTIATION; RECEPTOR; T(H)17; EXPRESSION; EFFECTOR; GENERATION AB Myeloid differentiation primary response protein 88 (MyD88) is classically known as an adaptor, linking TLR and IL-1R to downstream signaling pathways in the innate immune system. In addition to its role in innate immune cells, MyD88 has been shown to play an important role in T cells. How MyD88 regulates helper T-cell differentiation remains largely unknown, however. Here we demonstrate that MyD88 is an important regulator of IL-17-producing CD4(+) T helper cells (Th17) cell proliferation. MyD88-deficient CD4(+) T cells showed a defect in Th17 cell differentiation, but not in Th1 cell or Th2 cell differentiation. The impaired IL-17 production from MyD88-deficient CD4(+) T cells is not a result of defective RAR-related orphan receptor gamma t (ROR gamma t) expression. Instead, MyD88 is essential for sustaining the mammalian target of rapamycin (mTOR) activation necessary to promote Th17 cell proliferation by linking IL-1 and IL-23 signaling. MyD88-deficient CD4(+) T cells showed impaired mTOR activation and, consequently, reduced Th17 cell proliferation. Importantly, the absence of MyD88 in T cells ameliorated disease in the experimental autoimmune encephalomyelitis model. Taken together, our results demonstrate that MyD88 has a dual function in Th17 cells by delivering IL-1 signaling during the early differentiation stage and integrating IL-23 signaling to the mTOR complex to expand committed Th17 cells. C1 [Chang, JiHoon; Chang, Cheong-Hee] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Burkett, Patrick R.; Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Burkett, Patrick R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Pulm & Crit Care Div,Dept Med, Boston, MA 02115 USA. [Borges, Christopher M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Transplant Inst, Sch Med, Boston, MA 02215 USA. [Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Turka, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM lturka@partners.org; heechang@umich.edu FU National Institutes of Health [AI062789, AI073677] FX We thank Sang-Won V. Kim and Dan R. Littman (New York University, New York, NY) for the IL-23R retroviral vectors, Sei Yoshida and Ken Inoki (University of Michigan, Ann Arbor, MI) for helpful comments on mTOR signaling, and Ryan H. Newton (Beth Israel Deaconess Medical Center) for a critical reading of the manuscript. This work was supported by National Institutes of Health Grants AI062789 (to L. A. T.) and AI073677 (to C.-H.C.). NR 39 TC 27 Z9 30 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2270 EP 2275 DI 10.1073/pnas.1206048110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800065 PM 23341605 ER PT J AU Windahl, SH Borjesson, AE Farman, HH Engdahl, C Moverare-Skrtic, S Sjogren, K Lagerquist, MK Kindblom, JM Koskela, A Tuukkanen, J Pajevic, PD Feng, JQ Dahlman-Wright, K Antonson, P Gustafsson, JA Ohlsson, C AF Windahl, Sara H. Borjesson, Anna E. Farman, Helen H. Engdahl, Cecilia Moverare-Skrtic, Sofia Sjogren, Klara Lagerquist, Marie K. Kindblom, Jenny M. Koskela, Antti Tuukkanen, Juha Pajevic, Paola Divieti Feng, Jian Q. Dahlman-Wright, Karin Antonson, Per Gustafsson, Jan-Ake Ohlsson, Claes TI Estrogen receptor-alpha in osteocytes is important for trabecular bone formation in male mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OSTEOBLAST-LIKE CELLS; ANDROGEN RECEPTOR; KNOCKOUT MICE; FAS LIGAND; OLDER MEN; ER-ALPHA; BETA; DEFICIENT; ESTRADIOL; HEALTH AB The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-alpha (ER alpha), encoded by the Esr1 gene. ER alpha in osteoclasts is crucial for the trabecular bone-sparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ER alpha in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ER alpha(flox/flox) mice to generate mice lacking ER alpha protein expression specifically in osteocytes (Dmp1-ER alpha(-/-)). Male Dmp1-ER alpha(-/-) mice displayed a substantial reduction in trabecular bone volume (-20%, P < 0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (-45%, P < 0.01) but the number of osteoclasts per bone surface was unaffected in the male Dmp1-ER alpha(-/-) mice. The male Dmp1-ER alpha(-/-) mice had reduced expression of several osteoblast/osteocyte markers in bone, including Runx2, Sp7, and Dmp1 (P < 0.05). Gonadal intact Dmp1-ER alpha(-/-) female mice had no significant reduction in trabecular bone volume but ovariectomized Dmp1-ER alpha(-/-) female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment. Dmp1-ER alpha(-/-) mice of both genders had unaffected cortical bone. In conclusion, ER alpha in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ER alpha in osteocytes in males, but via ER alpha in osteoclasts in females. C1 [Windahl, Sara H.; Borjesson, Anna E.; Farman, Helen H.; Engdahl, Cecilia; Moverare-Skrtic, Sofia; Sjogren, Klara; Lagerquist, Marie K.; Kindblom, Jenny M.; Ohlsson, Claes] Univ Gothenburg, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Koskela, Antti; Tuukkanen, Juha] Univ Oulu, Dept Anat & Cell Biol, Inst Biomed, Oulu 90014, Finland. [Pajevic, Paola Divieti] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Feng, Jian Q.] Texas A&M Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX 75246 USA. [Dahlman-Wright, Karin; Antonson, Per; Gustafsson, Jan-Ake] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden. [Dahlman-Wright, Karin; Antonson, Per; Gustafsson, Jan-Ake] Karolinska Inst, Ctr Biosci Novum, S-14183 Huddinge, Sweden. [Gustafsson, Jan-Ake] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Dept Cell Biol & Biochem, Houston, TX 77204 USA. RP Gustafsson, JA (reprint author), Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden. EM jgustafsson@uh.edu; Claes.Ohlsson@medic.gu.se OI Lagerquist, Marie/0000-0002-9089-8605 FU Swedish Research Council; Swedish Cancer Fund; Swedish Foundation for Strategic Research; Swedish Combine Project; Avtal om Lakarutbildning och Forskning/Lakarutbildningsavtalet research grant in Gothenburg; Lundberg Foundation; Torsten and Ragnar Soderberg's Foundation; Novo Nordisk Foundation; National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) [DK071122]; Robert A. Welch Foundation [E-0004] FX This study was supported by the Swedish Research Council, the Swedish Cancer Fund, the Swedish Foundation for Strategic Research, the Swedish Combine Project, the Avtal om Lakarutbildning och Forskning/Lakarutbildningsavtalet research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation, the Novo Nordisk Foundation, the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases Grant DK071122), and the Robert A. Welch Foundation (E-0004). NR 34 TC 33 Z9 35 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2294 EP 2299 DI 10.1073/pnas.1220811110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800069 PM 23345419 ER PT J AU Yang, ZF Zhang, HJ Ma, LY Peng, C Chen, YY Wang, JL Green, MR Li, SG Rosmarin, AG AF Yang, Zhong-Fa Zhang, Haojian Ma, Leyuan Peng, Cong Chen, Yaoyu Wang, Junling Green, Michael R. Li, Shaoguang Rosmarin, Alan G. TI GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LSC; cell cycle control; signal transduction; imatinib ID CHRONIC MYELOID-LEUKEMIA; STEM-CELLS; GENE-EXPRESSION; MICE; PROGRESSION; ALPHA AB Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABP alpha and GABP beta proteins. Deletion in bone marrow of Gabpa, the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabp alpha prevented development of CML, although mice continued to generate BCR-ABL-expressing Gabp alpha-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabp alpha-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabp alpha-null BCR-ABL-expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia. C1 [Yang, Zhong-Fa; Zhang, Haojian; Peng, Cong; Chen, Yaoyu; Wang, Junling; Li, Shaoguang; Rosmarin, Alan G.] Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA 01655 USA. [Yang, Zhong-Fa] TaiShan Med Univ, Sch Basic Med Sci, Tai An 271016, Shandong, Peoples R China. [Zhang, Haojian] Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02215 USA. [Ma, Leyuan; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01655 USA. [Ma, Leyuan; Green, Michael R.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01655 USA. [Ma, Leyuan; Green, Michael R.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA. [Peng, Cong] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Peng, Cong] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chen, Yaoyu] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. RP Rosmarin, AG (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA 01655 USA. EM alan.rosmarin@umassmed.edu FU National Institutes of Health [R01 HL073945, R01 CA122142, CA 114199, GM 033977] FX We thank Xuejun Zhu, Karen Drumea, and James Cormier for technical assistance and Jonathan Licht, Lucio Castilla, and Glen Raffel for helpful discussions. We thank Cancer Research Technology Discovery Laboratories, Wolfson Institute for Biomedical Research, London WC1E 6BT, United Kingdom, for providing CRT0066101. This work was supported by National Institutes of Health Grants R01 HL073945 (to A. G. R.), R01 CA122142 (to S. L.), CA 114199 (to S. L.), and GM 033977 (to M. R. G.). M. R. G. is an investigator of the Howard Hughes Medical Institute. NR 20 TC 8 Z9 9 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 5 PY 2013 VL 110 IS 6 BP 2312 EP 2317 DI 10.1073/pnas.1212904110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093RQ UT WOS:000315209800072 PM 23345428 ER PT J AU Jensen, RA Sim, XL Li, XH Cotch, MF Ikram, MK Holliday, EG Eiriksdottir, G Harris, TB Jonasson, F Klein, BEK Launer, LJ Smith, AV Boerwinkle, E Cheung, N Hewitt, AW Liew, G Mitchell, P Wang, JJ Attia, J Scott, R Glazer, NL Lumley, T McKnight, B Psaty, BM Taylor, K Hofman, A de Jong, PTVM Rivadeneira, F Uitterlinden, AG Tay, WT Teo, YY Seielstad, M Liu, JJ Cheng, CY Saw, SM Aung, T Ganesh, SK O'Donnell, CJ Nalls, MA Wiggins, KL Kuo, JZ van Duijn, CM Gudnason, V Klein, R Siscovick, DS Rotter, JI Tai, ES Vingerling, J Wong, TY AF Jensen, Richard A. Sim, Xueling Li, Xiaohui Cotch, Mary Frances Ikram, M. Kamran Holliday, Elizabeth G. Eiriksdottir, Gudny Harris, Tamara B. Jonasson, Fridbert Klein, Barbara E. K. Launer, Lenore J. Smith, Albert Vernon Boerwinkle, Eric Cheung, Ning Hewitt, Alex W. Liew, Gerald Mitchell, Paul Wang, Jie Jin Attia, John Scott, Rodney Glazer, Nicole L. Lumley, Thomas McKnight, Barbara Psaty, Bruce M. Taylor, Kent Hofman, Albert de Jong, Paulus T. V. M. Rivadeneira, Fernando Uitterlinden, Andre G. Tay, Wan-Ting Teo, Yik Ying Seielstad, Mark Liu, Jianjun Cheng, Ching-Yu Saw, Seang-Mei Aung, Tin Ganesh, Santhi K. O'Donnell, Christopher J. Nalls, Mike A. Wiggins, Kerri L. Kuo, Jane Z. van Duijn, Cornelia M. Gudnason, Vilmundur Klein, Ronald Siscovick, David S. Rotter, Jerome I. Tai, E. Shong Vingerling, Johannes Wong, Tien Y. CA Blue Mt Eye Study GWAS Team CKDGen Consortium TI Genome-Wide Association Study of Retinopathy in Individuals without Diabetes SO PLOS ONE LA English DT Article ID RETINAL MICROVASCULAR ABNORMALITIES; ANTIHYPERTENSIVE DRUG THERAPIES; ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; CARDIOVASCULAR HEALTH; HYPERTENSION; COMMUNITIES; MORTALITY; DESIGN; STROKE AB Background: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes. Methods: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. Results: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3 +/- 0.23 (beta +/- standard error), p=6.6x10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (similar to 2%), the quality of the imputation was moderate (r(2) similar to 0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. Conclusions: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases. C1 [Jensen, Richard A.; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M.; Wiggins, Kerri L.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Jensen, Richard A.; Psaty, Bruce M.; Wiggins, Kerri L.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Sim, Xueling; Teo, Yik Ying] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Li, Xiaohui; Taylor, Kent; Kuo, Jane Z.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Ikram, M. Kamran; Tay, Wan-Ting; Cheng, Ching-Yu; Saw, Seang-Mei; Aung, Tin; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Ikram, M. Kamran; Vingerling, Johannes] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Holliday, Elizabeth G.; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Eiriksdottir, Gudny; Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Jonasson, Fridbert; Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland. [Jonasson, Fridbert] Landspitalinn Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Cheung, Ning; Hewitt, Alex W.; Liew, Gerald; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Liew, Gerald; Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia. [Liew, Gerald; Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Attia, John] John Hunter Hosp, Dept Med, Newcastle, NSW, Australia. [Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia. [Scott, Rodney] Univ Newcastle, Sch Biomed Sci, Newcastle, NSW 2300, Australia. [Glazer, Nicole L.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Vingerling, Johannes] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, Amsterdam, Netherlands. [de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands. [Teo, Yik Ying; Cheng, Ching-Yu; Saw, Seang-Mei; Tai, E. Shong] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Teo, Yik Ying] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Teo, Yik Ying; Liu, Jianjun] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Cheng, Ching-Yu; Saw, Seang-Mei; Aung, Tin; Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Nalls, Mike A.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Tai, E. Shong] Natl Univ Singapore, Singapore 117548, Singapore. [Tai, E. Shong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. RP Jensen, RA (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM richaj@uw.edu RI Cheng, Ching-Yu/K-7017-2013; Attia, John/F-5376-2013; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Hewitt, Alex/D-1936-2013; Cheung, Ning Danny/F-2043-2013; Gudnason, Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; OI Klein, Ronald/0000-0002-4428-6237; Ikram, Mohammad Kamran/0000-0003-0173-9571; Tai, E Shyong/0000-0003-2929-8966; Cheng, Ching-Yu/0000-0003-0655-885X; Attia, John/0000-0001-9800-1308; Wang, Jie Jin/0000-0001-9491-4898; Hewitt, Alex/0000-0002-5123-5999; Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Cotch, Mary Frances/0000-0002-2046-4350; Seielstad, Mark/0000-0001-5783-1401 FU National Institutes of Health (NIH) [N01-AG-12100]; National Institute on Aging Intramural Research Program at the NIH [ZIAAG007380, ZIAEY000401]; National Eye Institute Intramural Research Program at the NIH [ZIAAG007380, ZIAEY000401]; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; Australian National Health & Medical Research Council (NHMRC) [974159, 991407, 211069, 457349]; NHMRC [512423, 475604, 529912, 590204]; Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium; genotyping costs of the entire BMES population [085475/B/08/Z, 085475/08/Z]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; NHLBI [HL080295, HL075366, HL087652, HL105756, N02-HL-6-4278]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; Clinical Translational Science Institute [UL1RR033176]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR); Netherlands Organization of Scientific Research NWO [175.010.2005.011]; Erasmus Medical Center, Rotterdam; Erasmus University, Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII) the Netherlands; Municipality of Rotterdam; Lijf en Leven, Krimpen a/d Lek the Netherlands; MD Fonds, Utrecht the Netherlands; Oogfonds Nederland, Utrecht the Netherlands; Stichting Nederlands Oogheelkundig Onderzoek, Nijmegen/Rotterdam the Netherlands; Swart van Essen, Rotterdam the Netherlands; Netherlands Organisation for Scientific Research the Netherlands; Bevordering van Volkskracht, Rotterdam the Netherlands; Blindenhulp, The Hague the Netherlands; Rotterdamse Vereniging Blindenbelangen, Rotterdam the Netherlands; OOG, The Hague the Netherlands; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Doorn the Netherlands; Blinden-Penning, Amsterdam the Netherlands; Blindenhulp, 's Gravenzande the Netherlands; Henkes Stichting, Rotterdam the Netherlands; Topcon Europe BV, Capelle aan de IJssel the Netherlands; Medical Workshop BV, Groningen the Netherlands; [N01 HC-95159]; [N01-HC-95169]; [RR-024156] FX The authors declare that they have no relevant financial interests. Age, Gene/Environment Susceptibility-Reykjavik Study has been funded by National Institutes of Health (NIH) contract N01-AG-12100, the National Institute on Aging and National Eye Institute Intramural Research Programs at the NIH (ZIAAG007380 and ZIAEY000401), Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The Blue Mountains Eye Study (BMES) was supported by the Australian National Health & Medical Research Council (NHMRC) grants (IDs 974159, 991407, 211069 and 457349). The genome-wide association study was supported by the following grants: NHMRC project grants IDs 512423, 475604, 529912 and 590204, and funding by the Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 2 (A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster), which supported the genotyping costs of the entire BMES population (Grant numbers 085475/B/08/Z and 085475/08/Z). The Cardiovascular Health Study research was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants HL080295, HL075366, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by the Clinical Translational Science Institute grant UL1RR033176 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Additional funding was provided by the Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR). The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159 through N01-HC-95169 and RR-024156. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The GWA database of the Rotterdam Study was funded through the Netherlands Organization of Scientific Research NWO (nr. 175.010.2005.011).; The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The ophthalmologic part of the Rotterdam Study was supported by Lijf en Leven, Krimpen a/d Lek; MD Fonds, Utrecht. Oogfonds Nederland, Utrecht; Stichting Nederlands Oogheelkundig Onderzoek, Nijmegen/Rotterdam; Swart van Essen, Rotterdam; Netherlands Organisation for Scientific Research; Bevordering van Volkskracht, Rotterdam; Blindenhulp, The Hague; Rotterdamse Vereniging Blindenbelangen, Rotterdam; OOG, The Hague; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Doorn; Blinden-Penning, Amsterdam; Blindenhulp, 's Gravenzande; Henkes Stichting, Rotterdam; Topcon Europe BV, Capelle aan de IJssel; Medical Workshop BV, Groningen; all in the Netherlands; Heidelberg Engineering, Dossenheim, Germany. The Singapore Indian Eye Study was funded by grants from the Biomedical Research Council of Singapore (BMRC 09/1/35/19/616 and BMRC 08/1/35/19/550) and the National Medical Research Council of Singapore (NMRC/STaR/0003/2008). The Singapore BioBank and the Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore provided services for tissue archival and genotyping. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 5 Z9 5 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 5 PY 2013 VL 8 IS 2 AR e54232 DI 10.1371/journal.pone.0054232 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086NV UT WOS:000314692800009 PM 23393555 ER PT J AU Raeder, MB Birkeland, E Trovik, J Krakstad, C Shehata, S Schumacher, S Zack, TI Krohn, A Werner, HMJ Moody, SE Wik, E Stefansson, IM Holst, F Oyan, AM Tamayo, P Mesirov, JP Kalland, KH Akslen, LA Simon, R Beroukhim, R Salvesen, HB AF Raeder, Maria B. Birkeland, Even Trovik, Jone Krakstad, Camilla Shehata, Shyemaa Schumacher, Steven Zack, Travis I. Krohn, Antje Werner, Henrica M. J. Moody, Susan E. Wik, Elisabeth Stefansson, Ingunn M. Holst, Frederik Oyan, Anne M. Tamayo, Pablo Mesirov, Jill P. Kalland, Karl H. Akslen, Lars A. Simon, Ronald Beroukhim, Rameen Salvesen, Helga B. TI Integrated Genomic Analysis of the 8q24 Amplification in Endometrial Cancers Identifies ATAD2 as Essential to MYC-Dependent Cancers SO PLOS ONE LA English DT Article ID PROGNOSTIC IMPACT; BREAST-CANCER; CARCINOMA; METASTASIS; MARKERS; GENE; INHIBITION; EXPRESSION; STRATEGY; TARGETS AB Chromosome 8q24 is the most commonly amplified region across multiple cancer types, and the typical length of the amplification suggests that it may target additional genes to MYC. To explore the roles of the genes most frequently included in 8q24 amplifications, we analyzed the relation between copy number alterations and gene expression in three sets of endometrial cancers (N = 252); and in glioblastoma, ovarian, and breast cancers profiled by TCGA. Among the genes neighbouring MYC, expression of the bromodomain-containing gene ATAD2 was the most associated with amplification. Bromodomain-containing genes have been implicated as mediators of MYC transcriptional function, and indeed ATAD2 expression was more closely associated with expression of genes known to be upregulated by MYC than was MYC itself. Amplifications of 8q24, expression of genes downstream from MYC, and overexpression of ATAD2 predicted poor outcome and increased from primary to metastatic lesions. Knockdown of ATAD2 and MYC in seven endometrial and 21 breast cancer cell lines demonstrated that cell lines that were dependent on MYC also depended upon ATAD2. These same cell lines were also the most sensitive to the histone deacetylase (HDAC) inhibitor Trichostatin-A, consistent with prior studies identifying bromodomain-containing proteins as targets of inhibition by HDAC inhibitors. Our data indicate high ATAD2 expression is a marker of aggressive endometrial cancers, and suggest specific inhibitors of ATAD2 may have therapeutic utility in these and other MYC-dependent cancers. C1 [Raeder, Maria B.; Birkeland, Even; Trovik, Jone; Krakstad, Camilla; Werner, Henrica M. J.; Wik, Elisabeth; Salvesen, Helga B.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Raeder, Maria B.; Birkeland, Even; Trovik, Jone; Krakstad, Camilla; Werner, Henrica M. J.; Wik, Elisabeth; Salvesen, Helga B.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Raeder, Maria B.; Shehata, Shyemaa; Schumacher, Steven; Zack, Travis I.; Moody, Susan E.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Raeder, Maria B.; Shehata, Shyemaa; Schumacher, Steven; Zack, Travis I.; Moody, Susan E.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schumacher, Steven; Zack, Travis I.; Moody, Susan E.; Tamayo, Pablo; Mesirov, Jill P.; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Zack, Travis I.] Harvard Univ, Dept Biophys, Boston, MA 02115 USA. [Krohn, Antje; Holst, Frederik; Simon, Ronald] Univ Med Ctr Hamburg Eppendorf, Dept Pathol, Hamburg, Germany. [Stefansson, Ingunn M.; Oyan, Anne M.; Kalland, Karl H.; Akslen, Lars A.] Univ Bergen, Gade Inst, Bergen, Norway. [Stefansson, Ingunn M.; Akslen, Lars A.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Oyan, Anne M.; Kalland, Karl H.] Haukeland Hosp, Dept Microbiol & Immunol, N-5021 Bergen, Norway. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Raeder, MB (reprint author), Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. EM Maria.Rader@uib.no RI Schumacher, Steven/E-9821-2013; Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017; OI Schumacher, Steven/0000-0002-6819-5647; Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831; Holst, Frederik/0000-0002-5928-2175; Simon, Ronald/0000-0003-0158-4258; Krakstad, Camilla/0000-0002-0174-8139 FU Helse Vest [990172, 911351, 911624, 911626]; University of Bergen; Norwegian Cancer Society; Research Council of Norway [205404, 193373]; National Cancer Institute [K08CA122833, U54CA143798]; V Foundation Scholarship FX Financial support: Helse Vest Grants 990172 (MBR), 911351, 911624, and 911626 (HBS); the University of Bergen; the Norwegian Cancer Society; the Research Council of Norway Grants 205404 and 193373 (HBS); the National Cancer Institute (K08CA122833 and U54CA143798); and a V Foundation Scholarship (RB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 35 Z9 37 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 5 PY 2013 VL 8 IS 2 AR e54873 DI 10.1371/journal.pone.0054873 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086NV UT WOS:000314692800014 PM 23393560 ER PT J AU Wang, X Zhang, L O'Neill, A Bahamon, B Alsop, DC Mier, JW Goldberg, SN Signoretti, S Atkins, MB Wood, CG Bhatt, RS AF Wang, X. Zhang, L. O'Neill, A. Bahamon, B. Alsop, D. C. Mier, J. W. Goldberg, S. N. Signoretti, S. Atkins, M. B. Wood, C. G. Bhatt, R. S. TI Cox-2 inhibition enhances the activity of sunitinib in human renal cell carcinoma xenografts SO BRITISH JOURNAL OF CANCER LA English DT Article DE renal cell carcinoma; anti-angiogenic therapy; COX-2 inhibitor; sunitinib ID CYCLOOXYGENASE-2 INHIBITOR; INTERFERON-ALPHA; LUNG-CANCER; PHASE-II; SELECTIVE CYCLOOXYGENASE-2; ANTIANGIOGENIC THERAPY; EXPRESSION; CELECOXIB; RESISTANCE; APOPTOSIS AB Background: Sunitinib (Su), a tyrosine kinase inhibitor of VEGFR, is effective at producing tumour response in clear cell renal cell carcinoma (cRCC), but resistance to therapy is inevitable. As COX-2 is a known mediator of tumour growth, we explored the potential benefit of COX-2 inhibition in combination with VEGFR inhibition in attempts at delaying tumour progression on Su. Methods: COX-2 expression was compared with areas of hypoxia in tumours that progressed on Su vs untreated tumours. Mice bearing human cRCC xenografts were treated with Su and the COX-2 inhibitor, celecoxib, and the effects on tumour growth were assessed. Sequential vs concurrent regimens were compared. Results: COX-2 expression was increased in cRCC xenografts in areas of tumour hypoxia. The combination of Su and celecoxib achieved longer times to tumour progression compared to treatment with either agent alone or to untreated control animals in four models. This effect was seen with concurrent but not with sequential therapy. Conclusion: COX-2 inhibition can extend the effectiveness of VEGFR inhibition. This effect is dependent on the timing of therapy. Clinical trials combining Su and COX-2 inhibitors should be considered as a means delaying time to progression on sunitinib in patients with metastatic cRCC. C1 [Wang, X.; Alsop, D. C.; Goldberg, S. N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Wang, X.; Zhang, L.; Mier, J. W.; Bhatt, R. S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. [O'Neill, A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bahamon, B.; Signoretti, S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Goldberg, S. N.] Hadassah Hebrew Univ, Dept Radiol, Med Ctr, IL-91120 Jerusalem, Israel. [Atkins, M. B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Wood, C. G.] Univ Texas MD Anderson Canc Ctr, Div Surg, Dept Urol, Houston, TX 77030 USA. RP Bhatt, RS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol & Canc Biol, 330 Brookline Ave, Boston, MA 02215 USA. EM rbhatt@bidmc.harvard.edu RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 FU National Institutes of Health/National Cancer Institute [5 K08 CA138900]; Dana-Farber/Harvard Cancer Centre Kidney SPORE National Cancer Institute [P50CA101942] FX This work was supported by research grants awarded to RB from the National Institutes of Health/National Cancer Institute (5 K08 CA138900) and the Dana-Farber/Harvard Cancer Centre Kidney SPORE National Cancer Institute (P50CA101942). NR 39 TC 15 Z9 16 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 5 PY 2013 VL 108 IS 2 BP 319 EP 326 DI 10.1038/bjc.2012.591 PG 8 WC Oncology SC Oncology GA 087YP UT WOS:000314800900011 PM 23322198 ER PT J AU Butler, J Subacius, H Vaduganathan, M Fonarow, GC Ambrosy, AP Konstam, MA Maggioni, A Mentz, RJ Swedberg, K Zannad, F Gheorghiade, M AF Butler, Javed Subacius, Haris Vaduganathan, Muthiah Fonarow, Gregg C. Ambrosy, Andrew P. Konstam, Marvin A. Maggioni, Aldo Mentz, Robert J. Swedberg, Karl Zannad, Faiez Gheorghiade, Mihai CA EVEREST Investigators TI Relationship Between Clinical Trial Site Enrollment With Participant Characteristics, Protocol Completion, and Outcomes Insights From the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute heart failure; clinical trials; outcomes assessment; quality of care AB Objectives The study investigated whether the number of participants enrolled per site in an acute heart failure trial is associated with participant characteristics and outcomes. Background Whether and how site enrollment volume affects clinical trials is not known. Methods A total of 4,133 participants enrolled among 359 sites were grouped on the basis of total enrollment into 1 to 10, 11 to 30, and >30 participants per site and were compared for outcomes (cardiovascular mortality or heart failure hospitalization). Results Per-site enrollment ranged from 0 to 75 (median 6; 77 sites had no enrollment). Regional differences in enrollment were noted between North and South America, and Western and Eastern Europe (p < 0.001). Participants from sites with fewer enrollments were more likely to be older and male, have lower ejection fraction and blood pressure as well as worse comorbidity and laboratory profile, and were less likely to be on angiotensin-converting enzyme inhibitors or aldosterone antagonists. During a median follow-up of 9.9 months, 1,700 (41%) participants had an outcome event. Compared to event rate at sites with >30 participants (32%), those with 1 to 10 (51%, hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.56 to 2.02) and 11 to 30 (42%, HR: 1.44, 95% CI: 1.28 to 1.62) participants per site groups had worse outcomes. This relationship was comparable across regions (p = 0.43). After adjustment for risk factors, participants enrolled at sites with fewer enrollees were at higher risk for adverse outcomes (HR: 1.26, 95% CI: 1.08 to 1.46 for 1 to 10; HR: 1.22, 95% CI: 1.07 to 1.38 for 11 to 30 vs. >30 participant sites). Higher proportion of participants from site with >30 participants completed the protocol (45.5% for <10, 61.7% for 11 to 30, and 68.4% for sites enrolling >30 participants; p < 0.001). Conclusions Baseline characteristics, protocol completion, and outcomes differed significantly among higher versus lower enrolling sites. These data imply that the number of participant enrolled per site may influence trials beyond logistics. (J Am Coll Cardiol 2013; 61: 571-9) (C) 2013 by the American College of Cardiology Foundation C1 [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Subacius, Haris; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Ambrosy, Andrew P.] Stanford Univ, Palo Alto, CA 94304 USA. [Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA. [Konstam, Marvin A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Maggioni, Aldo] ANMCO Res Ctr, Florence, Italy. [Mentz, Robert J.] Duke Univ, Durham, NC USA. [Swedberg, Karl] Univ Gothenburg, Gothenburg, Sweden. [Zannad, Faiez] INSERM, CIC 9501, Nancy, France. [Zannad, Faiez] CHU Nancy, Inst Lorrain Coeur & Vaisseaux, U961, Nancy, France. [Zannad, Faiez] Univ Lorraine, Nancy, France. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Agency for Healthcare Research and Quality; Merck; Otsuka; Johnson Johnson; Amgen; Novartis; Cardiokine; Medtronic; Gilead Sciences; AstraZeneca; Servier; Bayer Schering Pharma AG; DebioPharm S.A.; Novartis Pharma AG; Otsuka Pharmaceuticals; Sigma Tau; Solvay Pharmaceuticals; Sticares InterACT; Takeda Pharmaceuticals North America, Inc. FX Dr. Fonarow receives research support from the Agency for Healthcare Research and Quality and serves as a consultant for Medtronic and Novartis. Dr. Konstam has received research support and/or served as a consultant for Merck, Otsuka, Johnson & Johnson, Amgen, Novartis, and Cardiokine. Dr. Maggioni receives honoraria from Otsuka. Dr. Mentz has received grants from Medtronic and research funding from Gilead Sciences. Dr. Swedberg receives research grants from AstraZeneca, Servier, and Amgen; honoraria from AstraZeneca, Otsuka, Servier, and Amgen; and is a consultant for Cytokinetics, Servier, and Novartis. Dr. Zannad has received honoraria from and served on advisory boards for Pfizer Inc. Dr. Gheorghiade has a relationship with Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG, Cardiorentis Ltd, Corthera, Cytokinetics, CytoPherx, Inc., DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, Inc., Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Ono Pharmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, PeriCor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals North America, Inc., and Trevena Therapeutics; and has received support from Bayer Schering Pharma AG, DebioPharm S.A., Medtronic, Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, and Takeda Pharmaceuticals North America, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 25 TC 32 Z9 32 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 5 PY 2013 VL 61 IS 5 BP 571 EP 579 DI 10.1016/j.jacc.2012.10.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086BZ UT WOS:000314659300010 PM 23246389 ER PT J AU Bhatt, DL Cavender, MA AF Bhatt, Deepak L. Cavender, Matthew A. TI Are All Clinical Trial Sites Created Equal? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE acute heart failure; clinical trials; quality of care and outcomes assessment ID ELEVATION MYOCARDIAL-INFARCTION; HEART-FAILURE; OUTCOMES; TOLVAPTAN; EVEREST C1 [Bhatt, Deepak L.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.; Cavender, Matthew A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Cavender, Matthew A.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, 75 Francis St,PBB 146, Boston, MA 02115 USA. EM DLBHATTMD@post.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 5 PY 2013 VL 61 IS 5 BP 580 EP 581 DI 10.1016/j.jacc.2012.10.024 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086BZ UT WOS:000314659300011 PM 23246386 ER PT J AU Wynn, JK Mathis, KI Ford, J Breitmeyer, BG Green, MF AF Wynn, Jonathan K. Mathis, Kristopher I. Ford, Judith Breitmeyer, Bruno G. Green, Michael F. TI Object substitution masking in schizophrenia: an event-related potential analysis SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE visual processing; schizophrenia; ERP; visual backward masking; reentrant processing ID PSYCHIATRIC RATING-SCALE; BACKWARD VISUAL MASKING; PROCESSING DEFICITS; SENSORY CONTRIBUTIONS; RECOGNITION AREAS; QUALITY-ASSURANCE; AWARENESS; PERCEPTION; ATTENTION; ERP AB Schizophrenia patients exhibit deficits on visual processing tasks, including visual backward masking, and these impairments are related to deficits in higher-level processes. In the current study we used electroencephalography techniques to examine successive stages and pathways of visual processing in a specialized masking paradigm, four-dot masking, which involves masking by object substitution. Seventy-six schizophrenia patients and 66 healthy controls had event-related potentials (ERPs) recorded during four-dot masking. Target visibility was manipulated by changing stimulus onset asynchrony (SOA) between the target and mask, such that performance decreased with increasing SOA. Three SOAs were used: 0, 50, and 100 ms. The P100 and N100 perceptual ERPs were examined. Additionally, the visual awareness negativity (VAN) to correct vs. incorrect responses, an index of reentrant processing, was examined for SOAs 50 and 100 ms. Results showed that patients performed worse than controls on the behavioral task across all SOAs. The ERP results revealed that patients had significantly smaller P100 and N100 amplitudes, though there was no effect of SOA on either component in either group. In healthy controls, but not patients, N100 amplitude correlated significantly with behavioral performance at SOAs where masking occurred, such that higher accuracy correlated with a larger N100. Healthy controls, but not patients, exhibited a larger VAN to correct vs. incorrect responses. The results indicate that the N100 appears to be related to attentional effort in the task in controls, but not patients. Considering that the VAN is thought to reflect reentrant processing, one interpretation of the findings is that patients' lack of VAN response and poorer performance may be related to dysfunctional reentrant processing. C1 [Wynn, Jonathan K.; Mathis, Kristopher I.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Ford, Judith] San Francisco VA Med Ctr, San Francisco, CA USA. [Ford, Judith] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Breitmeyer, Bruno G.] Univ Houston, Dept Psychol, Houston, TX USA. RP Wynn, JK (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [R01 MH043292, R01 MH065707, R29 MH043292] NR 64 TC 2 Z9 2 U1 0 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD FEB 4 PY 2013 VL 4 AR 30 DI 10.3389/fpsyg.2013.00030 PG 9 WC Psychology, Multidisciplinary SC Psychology GA AA0KW UT WOS:000330785000001 PM 23382723 ER PT J AU Magge, R Lau, BC Soares, BP Fischette, S Arora, S Tong, E Cheng, S Wintermark, M AF Magge, R. Lau, B. C. Soares, B. P. Fischette, S. Arora, S. Tong, E. Cheng, S. Wintermark, M. TI Clinical Risk Factors and CT Imaging Features of Carotid Atherosclerotic Plaques as Predictors of New Incident Carotid Ischemic Stroke: A Retrospective Cohort Study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INTIMA-MEDIA THICKNESS; MULTIDETECTOR COMPUTED-TOMOGRAPHY; HIGH-RESOLUTION MRI; ARTERY STENOSIS; CARDIOVASCULAR HEALTH; SURFACE-MORPHOLOGY; CEREBRAL-ISCHEMIA; VIVO MRI; ENDARTERECTOMY; BIFURCATION AB BACKGROUND AND PURPOSE: Parameters other than luminal narrowing are needed to predict the risk of stroke more reliably, particularly in patients with <70% stenosis. The goal of our study was to identify clinical risk factors and CT features of carotid atherosclerotic plaques, in a retrospective cohort of patients free of stroke at baseline, that are independent predictors of incident stroke on follow-up. MATERIALS AND METHODS: We identified a retrospective cohort of patients admitted to our emergency department with suspected stroke between 2001-2007 who underwent a stroke work-up including a CTA of the carotid arteries that was subsequently negative for acute stroke. All patients also had to receive a follow-up brain study at least 2 weeks later. From a random sample, we reviewed charts and imaging studies of patients with subsequent new stroke on follow-up as well as those who remained stroke-free. All patients were classified either as new carotid infarct patients or no-new carotid infarct patients based on the Causative Classification for Stroke. Independently, the baseline CTA studies were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a set of carotid CT features (wall thickness, plaque ulcerations, fibrous cap thickness, lipid-rich necrotic core, and calcifications). Univariate and multivariate statistical analyses were used to identify any significant differences in CT features between the patient groups in the sample. Subsequent ROC analysis allowed comparison to the classic NASCET stenosis rule in identifying patients with incident stroke on follow-up. RESULTS: We identified a total of 315 patients without a new carotid stroke between baseline and follow-up, and 14 with a new carotid stroke between baseline and follow-up, creating the main comparison groups for the study. Statistical analysis showed age and use of antihypertensive drugs to be the most significant clinical variables, and maximal carotid wall thickness was the most relevant imaging variable. The use of age 75 years, antihypertensive medication use, and a maximal carotid wall thickness of at least 4 mm was able to successfully identify 10 of the 14 patients who developed a new incident infarct on follow-up. ROC analysis showed an area under the ROC curve of 0.706 for prediction of new stroke with this new model. CONCLUSIONS: Our new paradigm of using age 75 years, history of hypertension, and carotid maximal wall thickness of >4 mm identified most of the patients with subsequent new carotid stroke in our study. It is simple and may help clinicians choose the patients at greatest risk of developing a carotid infarct, warranting validation with a prospective observational study. C1 [Magge, R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Magge, R.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Lau, B. C.; Tong, E.; Wintermark, M.] Univ Virginia, Dept Radiol, Neuroradiol Div, Charlottesville, VA USA. [Soares, B. P.; Wintermark, M.] Univ Calif San Francisco, Dept Radiol, Neuroradiol Sect, San Francisco, CA 94143 USA. [Fischette, S.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Cheng, S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Arora, S.] Univ Louisville, Dept Radiol, Louisville, KY 40292 USA. RP Wintermark, M (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Radiol, Neuroradiol Div, Box 800170, Charlottesville, VA 22908 USA. EM Max.Wintermark@virginia.edu OI Wintermark, Max/0000-0002-6726-3951; Soares, Bruno/0000-0003-4185-6940 FU Doris Duke Clinical Research Fellowship; UCSF; Dana; NIH; Doris Duke; Dana Foundation; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [KL2 RR024130]; NIH Roadmap for Medical Research; National Institute of Neurological Disorders and Stroke, at the NIH [NS045085]; GE Healthcare FX Rajiv Magge-RELATED: Grant: Doris Duke Clinical Research Fellowship, Comments: Received financial support as clinical research fellow (during medical school; Support for Travel to Meetings for the Study or Other Purposes: Doris Duke Clinical Research Fellowship, Comments: Received travel support as clinical research fellow (during medical school). W. Scott Fischette-RELATED: Grant: UCSF Dean's Research Grant, Comments: Research grant provided by UCSF to medical students for summer research. Max Wintermark-RELATED: Grant: Dana,* NIH,* Doris Duke,* Comments: This research project was conducted with the support of a grant from the Dana Foundation (http://www.dana.org/). Max Wintermark was supported by Grant KL2 RR024130 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research, and by Grant NS045085 from the National Institute of Neurological Disorders and Stroke, at the NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the Dana Foundation, Doris Duke Charitable Foundation, NCRR or NIH; UNRELATED: Grant: GE Healthcare.* (*Money paid to institution) NR 43 TC 7 Z9 9 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2013 VL 34 IS 2 BP 402 EP 409 DI 10.3174/ajnr.A3228 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 282YH UT WOS:000329210300029 PM 22859283 ER PT J AU Vishwas, MS Healy, BC Pienaar, R Gorman, MP Grant, PE Chitnis, T AF Vishwas, M. S. Healy, B. C. Pienaar, R. Gorman, M. P. Grant, P. E. Chitnis, T. TI Diffusion Tensor Analysis of Pediatric Multiple Sclerosis and Clinically Isolated Syndromes SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID APPEARING WHITE-MATTER; FRACTIONAL ANISOTROPY; PROGNOSTIC-FACTORS; CORPUS-CALLOSUM; MRI CRITERIA; ONSET; CHILDHOOD; MS; DEMYELINATION; CHILDREN AB BACKGROUND AND PURPOSE: DTI has shown focal and diffuse white matter abnormalities in adults and children with MS. Here we explore whether DTI abnormalities are present at the time of a first attack or CIS in children and whether early DTI features can predict the development of MS. MATERIALS AND METHODS: We assessed region-of-interest and tract-based mean ADC and mean FA values for 3 major white matter pathways and NAWM in 20 children with MS, 27 children with forms of CIS, and controls. Tracts were selected by using standard region-of-interest placements on color FA maps. Identical ROIs were placed in the NAWM on b = 0 T2-weighted images to ensure that both ROIs and resulting tracts passed through NAWM. Conventional MR imaging characteristics were assessed by visual inspection. Statistical analysis compared FA and ADC values between groups by a t test. Logistic regression assessed the predictive value of DTI measures and published conventional MR imaging measures for conversion from CIS to MS. RESULTS: In pediatric patients with MS, all white matter pathways and analysis confined to the NAWM demonstrated higher mean ADC values and lower mean FA than in controls. In contrast, there were no significant differences in mean ADC and mean FA of white matter pathways in all CIS cohorts compared with controls. In the CIS cohort, none of the DTI measures in white matter pathways or in NAWM were significantly associated with conversion to RRMS in univariate or multivariate models (P > .05 in all models). CONCLUSIONS: There are significant anisotropic abnormalities in the NAWM of major tracts in children with MS. In contrast, there were no significant changes in pediatric patients with CIS compared with controls at baseline. DTI measures did not predict conversion to MS. The period between CIS and conversion to pediatric MS may represent a window of opportunity for the prevention of diffuse damage in the CNS and potentially progressive disability. C1 [Vishwas, M. S.; Gorman, M. P.; Chitnis, T.] Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, Boston, MA USA. [Vishwas, M. S.; Pienaar, R.; Grant, P. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, ACC 708,55 Fruit St, Boston, MA 02114 USA. EM tchitnis@partners.org FU Pediatric Multiple Sclerosis Centers of Excellence Grant from the National Multiple Sclerosis Society FX This work was supported by the Pediatric Multiple Sclerosis Centers of Excellence Grant from the National Multiple Sclerosis Society to T.C. NR 29 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2013 VL 34 IS 2 BP 417 EP 423 DI 10.3174/ajnr.A3216 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 282YH UT WOS:000329210300031 PM 22859275 ER PT J AU Silverman, MA Misasi, J Smole, S Feldman, HA Cohen, AB Santagata, S McManus, M Ahmed, AA AF Silverman, Michael A. Misasi, John Smole, Sandra Feldman, Henry A. Cohen, Adam B. Santagata, Sandro McManus, Michael Ahmed, Asim A. TI Eastern Equine Encephalitis in Children, Massachusetts and New Hampshire, USA, 1970-2010 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID INTRACRANIAL-PRESSURE; VIRUS; ENCEPHALOMYELITIS; CRANIECTOMY; OUTBREAK; VARIETY AB We describe the clinical, laboratory, and radiographic characteristics of 15 cases of eastern equine encephalitis in children during 1970-2010. The most common clinical and laboratory features were fever, headache, seizures, peripheral leukocytosis, and cerebrospinal fluid neutrophilic pleocytosis. Radiographic lesions were found in the basal ganglia, thalami, and cerebral cortex: Clinical outcomes included severe neurologic deficits in 5 (33%) patients, death of 4 (27%), full recovery of 4 (27%), and mild neurologic deficits in 2 (13%). We identify an association between a short prodrome and an increased risk for death or for severe disease. C1 [Silverman, Michael A.; Misasi, John; Feldman, Henry A.; Santagata, Sandro; McManus, Michael; Ahmed, Asim A.] Boston Childrens Hosp, Boston, MA USA. [Smole, Sandra] Dept Publ Hlth, Boston, MA USA. [Cohen, Adam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Santagata, Sandro] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ahmed, AA (reprint author), Dept Med, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM asim.ahmed@childrens.harvard.edu FU Fred Lovejoy Resident Research and Education Award; Child Health Research Center Fellowship; Boston Children's Hospital Faculty Development Award FX This work was supported by the Fred Lovejoy Resident Research and Education Award (M.A.S.) and by the Child Health Research Center Fellowship and the Boston Children's Hospital Faculty Development Award (A.A.A.). NR 25 TC 20 Z9 20 U1 0 U2 4 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2013 VL 19 IS 2 BP 194 EP 201 DI 10.3201/eid1902.120039 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268LT UT WOS:000328172900002 PM 23343480 ER PT J AU Elbogen, EB Wagner, HR Johnson, SC Kinneer, P Kang, H Vasterling, JJ Timko, C Beckham, JC AF Elbogen, Eric B. Wagner, H. Ryan Johnson, Sally C. Kinneer, Patricia Kang, Han Vasterling, Jennifer J. Timko, Christine Beckham, Jean C. TI Are Iraq and Afghanistan Veterans Using Mental Health Services? New Data From a National Random-Sample Survey SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WOMEN VETERANS; PERCEIVED BARRIERS; GUARD SOLDIERS; UNITED-STATES; PRIMARY-CARE; ACTIVE-DUTY; COMBAT; PREVALENCE; STIGMA AB Objective: This study analyzed data from a national survey of Iraq and Afghanistan veterans to improve understanding of mental health services use and perceived barriers. Methods: The National Post-Deployment Adjustment Survey randomly sampled post-9/11 veterans separated from active duty or in the Reserves or National Guard. The corrected response rate was 56% (N=1,388). Results: Forty-three percent screened positive for posttraumatic stress disorder (PTSD), major depression, or alcohol misuse. Past-year psychiatric treatment was reported by 69% of the PTSD group, 67% of the depression group, and 45% of those with alcohol misuse. Most received care at Veterans Affairs (VA) facilities, although women were more likely than men to seek non-VA services. Veterans with more severe symptoms reported greater treatment utilization. Eighteen percent saw a pastoral counselor (chaplain) in the past year. Veterans with mental health needs who did not access treatment were more likely to believe that they had to solve problems themselves and that medications would not help. Those who had accessed treatment were more likely to express concern about being seen as weak by others. Conclusions: Veterans in greatest need were more likely to access services. More than two-thirds with probable PTSD obtained past-year treatment, mostly at VA facilities. Treatment for veterans may be improved by increasing awareness of gender differences, integrating mental health and pastoral services, and recognizing that alcohol misuse may reduce utilization. Veterans who had and had not used services endorsed different perceptions about treatment, indicating that barriers to accessing care may be distinct from barriers to engaging in care. C1 [Elbogen, Eric B.; Johnson, Sally C.; Kinneer, Patricia] Univ North Carolina Chapel Hill, Dept Psychiat, Durham, NC 27599 USA. [Elbogen, Eric B.] Durham Vet Affairs VA Med Ctr, Durham, NC USA. [Wagner, H. Ryan; Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Kang, Han] Environm Epidemiol Serv, US Dept Vet Affairs, Washington, DC USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Dept Psychiat, Med Ctr, Boston, MA 02215 USA. [Timko, Christine] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Timko, Christine] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. RP Elbogen, EB (reprint author), Univ North Carolina Chapel Hill, Dept Psychiat, CB 7167, Durham, NC 27599 USA. EM eric.elbogen@unc.edu FU National Institute of Mental Health [R01MH080988]; Office of Research and Development Clinical Science and Health Services and Health Services, U.S. Department of Veterans Affairs (VA); VA's Mid-Atlantic Mental Illness Research, Education and Clinical Center FX Preparation of this report was supported by grant R01MH080988 from the National Institute of Mental Health and by the Office of Research and Development Clinical Science and Health Services, U.S. Department of Veterans Affairs (VA), and the VA's Mid-Atlantic Mental Illness Research, Education and Clinical Center. The authors extend sincere thanks to the participants who volunteered for this study. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the National Institutes of Health. NR 43 TC 54 Z9 54 U1 0 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD FEB PY 2013 VL 64 IS 2 BP 134 EP 141 DI 10.1176/appi.ps.004792011 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255SP UT WOS:000327260400012 PM 23475498 ER PT J AU Amin, ST Morrow, DA Braunwald, E Sloan, S Contant, C Murphy, S Antman, EM AF Amin, Sameer T. Morrow, David A. Braunwald, Eugene Sloan, Sarah Contant, Charles Murphy, Sabina Antman, Elliott M. TI Dynamic TIMI Risk Score for STEMI SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE coronary artery disease; mortality; myocardial infarction; prognosis ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; ATRIAL-FIBRILLATION; HEART-FAILURE; VENTRICULAR-TACHYCARDIA; CARDIOVASCULAR MEDICINE; PROGNOSTIC-SIGNIFICANCE; RECURRENT ISCHEMIA; GLOBAL REGISTRY; II TRIAL AB Background-Although there are multiple methods of risk stratification for ST-elevation myocardial infarction (STEMI), this study presents a prospectively validated method for reclassification of patients based on in-hospital events. A dynamic risk score provides an initial risk stratification and reassessment at discharge. Methods and Results-The dynamic TIMI risk score for STEMI was derived in ExTRACT-TIMI 25 and validated in TRITON-TIMI 38. Baseline variables were from the original TIMI risk score for STEMI. New variables were major clinical events occurring during the index hospitalization. Each variable was tested individually in a univariate Cox proportional hazards regression. Variables with P<0.05 were incorporated into a full multivariable Cox model to assess the risk of death at 1 year. Each variable was assigned an integer value based on the odds ratio, and the final score was the sum of these values. The dynamic score included the development of in-hospital MI, arrhythmia, major bleed, stroke, congestive heart failure, recurrent ischemia, and renal failure. The C-statistic produced by the dynamic score in the derivation database was 0.76, with a net reclassification improvement (NRI) of 0.33 (P<0.0001) from the inclusion of dynamic events to the original TIMI risk score. In the validation database, the C-statistic was 0.81, with a NRI of 0.35 (P=0.01). Conclusions-This score is a prospectively derived, validated means of estimating 1-year mortality of STEMI at hospital discharge and can serve as a clinically useful tool. By incorporating events during the index hospitalization, it can better define risk and help to guide treatment decisions. C1 [Amin, Sameer T.] Univ Calif Los Angeles, Dept Cardiol, Los Angeles, CA USA. [Morrow, David A.; Braunwald, Eugene; Sloan, Sarah; Murphy, Sabina; Antman, Elliott M.] Brigham & Womens Hosp, Dept Cardiol, TIMI Study Grp, Boston, MA 02115 USA. [Morrow, David A.; Braunwald, Eugene; Sloan, Sarah; Murphy, Sabina; Antman, Elliott M.] Harvard Univ, Boston, MA 02115 USA. [Contant, Charles] Tufts Clin & Translat Res Ctr, Boston, MA USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM eantman@partners.org FU Sanofi-Aventis; Daicchi Sankyo; Eli Lilly FX ExTRACT-TIMI 25 was supported by a research grant from Sanofi-Aventis, and TRITON-TIMI 38 was supported by research grants from Daicchi Sankyo and Eli Lilly. NR 41 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2013 VL 2 IS 1 AR UNSP e003269 DI 10.1161/JAHA.112.003269 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243SF UT WOS:000326336800002 PM 23525425 ER PT J AU Singer, DE Hellkamp, AS Piccini, JP Mahaffey, KW Lokhnygina, Y Pan, G Halperin, JL Becker, RC Breithardt, G Hankey, GJ Hacke, W Nessel, CC Patel, MR Califf, RM Fox, KAA AF Singer, Daniel E. Hellkamp, Anne S. Piccini, Jonathan P. Mahaffey, Kenneth W. Lokhnygina, Yuliya Pan, Guohua Halperin, Jonathan L. Becker, Richard C. Breithardt, Guenter Hankey, Graeme J. Hacke, Werner Nessel, Christopher C. Patel, Manesh R. Califf, Robert M. Fox, Keith A. A. CA ROCKET AF Investigators TI Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE anticoagulants; arrhythmia; embolism; prevention; risk factors ID NONVALVULAR ATRIAL-FIBRILLATION; NORMALIZED RATIO CONTROL; STROKE PREVENTION; ORAL ANTICOAGULATION; INTENSITY; QUALITY; RIVAROXABAN; DABIGATRAN; REGISTRY; VALUES AB Background-Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results-TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i-TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i-TTR was 55.2% (SD 21.3%) and the median i-TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i-TTR, dominant determinants were previous warfarin use (mean i-TTR of 61.1% for warfarin-experienced versus 47.4% in VKA-naive patients) and geographic region where patients were managed (mean i-TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i-TTRs had INR distributions shifted toward lower INR values and had longer inter-INR test intervals. Conclusions-Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i-TTR in global studies of warfarin. Regional differences in mean i-TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Becker, Richard C.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Piccini, Jonathan P.; Mahaffey, Kenneth W.; Becker, Richard C.; Patel, Manesh R.; Califf, Robert M.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27710 USA. [Pan, Guohua; Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Halperin, Jonathan L.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. [Breithardt, Guenter] Univ Hosp, Dept Cardiol & Angiol, Munster, Germany. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6001, Australia. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, S50-9, Boston, MA 02114 USA. EM dsinger@partners.org RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ); Bayer HealthCare AG (Leverkusen, Germany); Massachusetts General Hospital (Boston, MA) FX The ROCKET AF trial was supported by research grants from Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ) and Bayer HealthCare AG (Leverkusen, Germany). The Duke Clinical Research Institute (Durham, NC) coordinated the trial and performed the statistical analyses for this manuscript, independent of the sponsors. Dr Singer was supported, in part, by the Eliot B. and Edith C. Shoolman fund of Massachusetts General Hospital (Boston, MA). NR 25 TC 57 Z9 59 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2013 VL 2 IS 1 AR UNSP e000067 DI 10.1161/JAHA.112.000067 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243SF UT WOS:000326336800033 PM 23525418 ER PT J AU Smith, EE Shobha, N Dai, D Olson, DM Reeves, MJ Saver, JL Hernandez, AF Peterson, ED Fonarow, GC Schwamm, LH AF Smith, Eric E. Shobha, Nandavar Dai, David Olson, DaiWai M. Reeves, Mathew J. Saver, Jeffrey L. Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. Schwamm, Lee H. TI A Risk Score for In-Hospital Death in Patients Admitted With Ischemic or Hemorrhagic Stroke SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE intracerebral hemorrhage; ischemic stroke; mortality; subarachnoid hemorrhage ID QUALITY-OF-CARE; AMERICAN-HEART-ASSOCIATION; INTRACEREBRAL HEMORRHAGE; GUIDELINES-STROKE; SUBARACHNOID HEMORRHAGE; EXTERNAL VALIDATION; PREDICT MORTALITY; PROGNOSTIC MODELS; 30-DAY MORTALITY; GRADING SCALE AB Background-We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods and Results-Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. Conclusions-A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy. C1 [Smith, Eric E.; Shobha, Nandavar] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Dai, David; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Smith, EE (reprint author), Foothills Med Ctr, Room C1212,1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca RI Hernandez, Adrian F./A-7818-2016 OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Boeringher-Ingelheim; Merck FX The GWTG-Stroke program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim and Merck. NR 38 TC 16 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2013 VL 2 IS 1 AR UNSP e005207 DI 10.1161/JAHA.112.005207 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243SF UT WOS:000326336800034 PM 23525444 ER PT J AU Zamani, P Schwartz, GG Olsson, AG Rifai, N Bao, WH Libby, P Ganz, P Kinlay, S AF Zamani, Payman Schwartz, Gregory G. Olsson, Anders G. Rifai, Nader Bao, Weihang Libby, Peter Ganz, Peter Kinlay, Scott CA Myocardial Ischemia Reduction Aggr TI Inflammatory Biomarkers, Death, and Recurrent Nonfatal Coronary Events After an Acute Coronary Syndrome in the MIRACL Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndromes; biomarkers; CRP; death; nonfatal events; risk ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; ACUTE-PHASE PROTEINS; LONG-TERM MORTALITY; UNSTABLE ANGINA; ARTERY-DISEASE; PROGNOSTIC VALUE; TROPONIN-T; RISK; ELEVATION AB Background-In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome. Methods and Results-We measured blood concentrations of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), soluble intercellular adhesion molecule (ICAM), soluble vascular cell adhesion molecule (VCAM), E-selectin, P-selectin, and tissue plasminogen activator antigen (tPA) 24 to 96 hours after presentation with acute coronary syndrome in 2925 subjects participating in a multicenter study. Biomarkers were related to the risk of death, and recurrent nonfatal acute coronary syndromes (myocardial infarction or unstable angina) over 16 weeks using Cox proportional hazard models. On univariate analyses, baseline CRP (P=0.006), SAA (P=0.012), and IL-6 (P<0.001) were related to death, but not to recurrent nonfatal acute coronary syndromes. VCAM and tPA related to the risk of death (P<0.001, P=0.021, respectively) and to nonfatal acute coronary syndromes (P=0.021, P=0.049, respectively). Adjusting for significant covariates reduced the strength of the associations; however, CRP and SAA continued to relate to death. Conclusions-In acute coronary syndromes, the CRP inflammatory axis relates to the risk of death and may reflect myocardial injury. VCAM and tPA may have greater specificity for processes reflecting inflammation and thrombosis in the epicardial arteries, which determine recurrent coronary events. C1 [Zamani, Payman] Hosp Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. [Schwartz, Gregory G.] Univ Colorado, Vet Affairs Med Ctr, Div Cardiol, Denver, CO 80202 USA. [Olsson, Anders G.] Linkoping Univ, Fac Hlth Sci, Linkoping, Sweden. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Bao, Weihang] Pfizer Pharmaceut Grp, New York, NY USA. [Ganz, Peter] San Francisco Gen Hosp, Div Cardiovasc, San Francisco, CA 94110 USA. [Ganz, Peter] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Libby, Peter; Kinlay, Scott] VA Boston Healthcare Syst, Brigham & Womens Hosp, Div Cardiovasc, West Roxbury, MA 02132 USA. [Rifai, Nader; Libby, Peter; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM scott.kinlay@va.gov FU Pfizer, Inc. FX This study was supported by an unrestricted grant from Pfizer, Inc. NR 32 TC 21 Z9 26 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2013 VL 2 IS 1 AR UNSP e003103 DI 10.1161/JAHA.112.003103 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243SF UT WOS:000326336800041 PM 23525424 ER PT J AU Garcia-Godoy, F Kao, LM Flaitz, CM Hicks, J AF Garcia-Godoy, Franklin Kao, Lisa Marie Flaitz, Catherine M. Hicks, John TI Fluoride dentifrice containing xylitol: In vitro root caries formation SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID 0.243-PERCENT SODIUM-FLUORIDE; MUTANS STREPTOCOCCI; LASER IRRADIATION; DENTAL ENAMEL; BIOCHEMICAL-MECHANISM; ANTICARIES EFFICACY; 10-PERCENT XYLITOL; SURFACE CARIES; ORAL BACTERIA; REMINERALIZATION AB Purpose: To evaluate the effects of experimental xylitol dentifrices with and without fluoride on in vitro root caries formation. Methods: Root surfaces from caries-free human permanent teeth (n=10) underwent debridement and a fluoride-free prophylaxis. The tooth roots were sectioned into quarters, and acid-resistant varnish was placed with two sound root surface windows exposed on each tooth quarter. Each quarter from a single tooth was assigned to a treatment group: (1) No treatment control; (2) Aquafresh Advanced (0.15% F = 1,150 ppm F); (3) Experimental xylitol dentifrice without fluoride (0.45% xylitol); and (4) Diamynt fluoride dentifrice with xylitol (0.83% sodium monofluorophosphate = 1,100 ppm F and 0.20% xylitol). Tooth root quarters were treated with fresh dentifrice twice daily (3 minutes) followed by fresh synthetic saliva rinsing over a 7-day period. Controls were exposed twice daily to fresh synthetic saliva rinsing daily over a 7-day period. In vitro root caries were created using an acidified gel (pH 4.25, 21 days). Longitudinal sections (three sections/tooth quarter, 60/group) were evaluated for mean lesion depths (water inhibition, polarized light, ANOVA, DMR). Results: Mean lesion depths were 359 +/- 37 mu m for the control Group; 280 +/- 28 mu m for Aquafresh Advanced; 342 +/- 41 mu m for the experimental xylitol dentifrice without fluoride; and 261 +/- 34 pm for Diamynt. Aquafresh Advanced and Diamynt had mean lesion depths significantly less than those for the no treatment control and the experimental xylitol without fluoride dentifrice (P< 0.05). There were minimal non-significant differences in mean lesion depths between Aquafresh Advanced and Diamynt (P> 0.05). C1 [Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Hlth Sci Ctr, Memphis, TN 38163 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Cambridge, MA USA. [Kao, Lisa Marie] LMKao LLC, New York, NY USA. [Flaitz, Catherine M.] Univ Texas Houston, Sch Dent, Dept Diagnost & Biomed Sci, Houston, TX USA. [Flaitz, Catherine M.] Univ Texas Houston, Dept Pediat Dent, Sch Dent, Houston, TX USA. [Flaitz, Catherine M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Oncol, Houston, TX 77030 USA. [Hicks, John] Texas Childrens Hosp, Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Hicks, John] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat Hematol & Oncol, Houston, TX 77030 USA. [Hicks, John] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Pediat Dent, Houston, TX 77030 USA. RP Garcia-Godoy, F (reprint author), Univ Tennessee, Coll Dent, Biosci Res Ctr, Hlth Sci Ctr, 875 Union Ave, Memphis, TN 38163 USA. EM fgarciagodoy@gmail.com NR 61 TC 0 Z9 0 U1 1 U2 4 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD FEB PY 2013 VL 26 IS 1 BP 56 EP 60 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 233UX UT WOS:000325596100010 PM 23724551 ER PT J AU Shyti, R Eikermann-Haerter, K Meijer, OC van Heiningen, SH De Groote, L Ferrari, MD Ayata, C van den Maagdenberg, AMJ Tolner, EA AF Shyti, R. Eikermann-Haerter, K. Meijer, O. C. van Heiningen, S. H. De Groote, L. Ferrari, M. D. Ayata, C. van den Maagdenberg, A. M. J. Tolner, E. A. TI Corticosterone enhances CSD susceptibility via glucocorticoid receptor activation in familial hemiplegic migraine 1 Cacna1a knock-in mice SO JOURNAL OF HEADACHE AND PAIN LA English DT Meeting Abstract ID SPREADING DEPRESSION C1 [Shyti, R.; van Heiningen, S. H.; van den Maagdenberg, A. M. J.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Eikermann-Haerter, K.; Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Neurol, Boston, MA USA. [Meijer, O. C.] Leiden Univ, Dept Endocrinol, Med Ctr, Leiden, Netherlands. [De Groote, L.; Tolner, E. A.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [Ferrari, M. D.] Dept Neurol, Leiden, Netherlands. NR 2 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 1129-2369 EI 1129-2377 J9 J HEADACHE PAIN JI J. Headache Pain PD FEB PY 2013 VL 14 SU 1 AR P85 DI 10.1186/1129-2377-14-S1-P85 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 232WR UT WOS:000325525600103 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Racial and Gender Disparities Among Patients with Gout SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE Gout; Hyperuricemia; Race; Ethnicity; Gender; Disparity; Epidemiology; Prevalence; Genetic risk factors; Adverse effects ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; UNITED-STATES; URIC-ACID; AFRICAN-AMERICAN; SEX-DIFFERENCES; HEALTH-CARE; PHYSICIAN COMMUNICATION; RACE/ETHNIC DISPARITY AB Gout affects 8.3 million Americans according to NHANES 2007-2008, approximately 3.9 % of the US population. Gout has substantial effect on physical function, productivity, health-related quality of life (HRQOL), and health care costs. Uncontrolled gout is also associated with significant use of emergency care services. Women are less likely to have gout than men, but in the postmenopausal years the gender difference in disease incidence decreases. Compared with whites, racial and/or ethnic minorities, especially blacks, have higher prevalence of gout. Blacks are also less likely to receive quality gout care, leading to disproportionate morbidity. Women are less likely than men to receive allopurinol, and less likely to undergo joint aspirations for crystal analysis to establish diagnosis, but those on urate-lowering therapy are as likely as, or more likely than, men to undergo serum urate check within six months of initiation. Although a few studies provide the knowledge related to gender and race and/or ethnicity disparities for gout, several knowledge gaps exist in gout epidemiology and outcomes differences by gender and race and/or ethnicity. These should be investigated in future studies. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Div Rheumatol, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institute of Aging; National Cancer Institute; National Institute of Arthritis and Musculoskeletal Diseases; Agency for Health Quality; Research Center for Education and Research on Therapeutics FX Dr Singh is supported by research grants from the National Institute of Aging, the National Cancer Institute, the National Institute of Arthritis and Musculoskeletal Diseases, the Agency for Health Quality, and the Research Center for Education and Research on Therapeutics, and by the resources and facilities at the Birmingham VA Medical Center, Alabama, USA. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 79 TC 21 Z9 21 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD FEB PY 2013 VL 15 IS 2 AR 307 DI 10.1007/s11926-012-0307-x PG 9 WC Rheumatology SC Rheumatology GA 225VT UT WOS:000324993800004 PM 23315156 ER PT J AU Bhuvaneswar, CG Stern, TA AF Bhuvaneswar, Chaya G. Stern, Theodore A. TI Teaching cross-cultural aspects of mourning: A Hindu perspective on death and dying SO PALLIATIVE & SUPPORTIVE CARE LA English DT Editorial Material ID SUICIDE C1 [Bhuvaneswar, Chaya G.] Covance Inc, Dept Neurosci, Princeton, NJ USA. [Bhuvaneswar, Chaya G.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Bhuvaneswar, CG (reprint author), Covance Inc, Dept Neurosci, Princeton, NJ USA. EM chayab77@gmail.com NR 26 TC 0 Z9 0 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD FEB PY 2013 VL 11 IS 1 BP 79 EP 84 DI 10.1017/S1478951512000946 PG 6 WC Health Policy & Services SC Health Care Sciences & Services GA 219VP UT WOS:000324539500009 PM 23171885 ER PT J AU Courtwright, A AF Courtwright, Andrew TI From Unregulated Practice to Credentialed Profession: Implementing Ethics Consultation Competencies SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Courtwright, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Courtwright, A (reprint author), Massachusetts Gen Hosp, Inst Patient Care, 55 Fruit St, Boston, MA 02114 USA. EM acourt1500@gmail.com NR 4 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD FEB 1 PY 2013 VL 13 IS 2 BP 16 EP 17 DI 10.1080/15265161.2012.750389 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 189YG UT WOS:000322303600004 PM 23391051 ER PT J AU Fox, MD Liu, HS Pascual-Leone, A AF Fox, Michael D. Liu, Hesheng Pascual-Leone, Alvaro TI Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity SO NEUROIMAGE LA English DT Article DE Transcranial magnetic stimulation; TMS; Intrinsic connectivity; Resting state functional connectivity; MRI; Subgenual; Dorsolateral prefrontal cortex; Depression; Individual differences; Variability; Seed map ID TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; DORSOLATERAL PREFRONTAL CORTEX; TEST-RETEST RELIABILITY; HUMAN CEREBRAL-CORTEX; FUNCTIONAL CONNECTIVITY; BRAIN CONNECTIVITY; ANTERIOR CINGULATE; MAJOR DEPRESSION; MOTOR CORTEX AB Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression however outcomes vary greatly between patients. We have shown that average clinical efficacy of different left DLPFC TMS sites is related to intrinsic functional connectivity with remote regions including the subgenual cingulate and suggested that functional connectivity with these remote regions might be used to identify optimized left DLPFC targets for TMS. However it remains unclear if and how this connectivity-based targeting approach should be applied at the single-subject level to potentially individualize therapy to specific patients. In this article we show that individual differences in DLPFC connectivity are large, reproducible across sessions, and can be used to generate individualized DLPFC TMS targets that may prove clinically superior to those selected on the basis of group-average connectivity. Factors likely to improve individualized targeting including the use of seed maps and the focality of stimulation are investigated and discussed. The techniques presented here may be applicable to individualized targeting of focal brain stimulation across a range of diseases and stimulation modalities and can be experimentally tested in clinical trials. (C) 2012 Elsevier Inc. All rights reserved. C1 [Fox, Michael D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fox, Michael D.; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Fox, Michael D.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Michael D.; Liu, Hesheng] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Hosp Neurorehabil, Inst Guttmann, E-08193 Barcelona, Spain. RP Fox, MD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM foxmdphd@gmail.com OI Liu, Hesheng/0000-0002-7233-1509 FU National Institutes of Health [R25NS065743, K25NS069805]; National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758] FX We thank the Brain Genomics Superstruct Project for contributing data and David Alsop for assistance with MRI acquisition and sequence optimization for the depression patients. MDF was supported by NIH grant R25NS065743 and HL by NIH grant K25NS069805. APL serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neuroelectrics, Neosync, and Novavision, and is listed as inventor in issued patents and patent applications on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). Work on this study was also supported by grants from the National Institutes of Health and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758). NR 64 TC 32 Z9 34 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2013 VL 66 BP 151 EP 160 DI 10.1016/j.neuroimage.2012.10.082 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 190QR UT WOS:000322355800016 PM 23142067 ER PT J AU Bernal-Rusiel, JL Greve, DN Reuter, M Fischl, B Sabuncu, MR AF Bernal-Rusiel, Jorge L. Greve, Douglas N. Reuter, Martin Fischl, Bruce Sabuncu, Mert R. CA Alzheimer's Dis Neuroimaging Initi TI Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models SO NEUROIMAGE LA English DT Article DE Longitudinal studies; Linear Mixed Effects models; Statistical analysis ID MILD COGNITIVE IMPAIRMENT; BRAIN VOLUME CHANGES; SURFACE-BASED ANALYSIS; GRAY-MATTER VOLUME; ALZHEIMERS-DISEASE; HIPPOCAMPAL ATROPHY; CORTICAL THICKNESS; 1ST-EPISODE SCHIZOPHRENIA; MAXIMUM-LIKELIHOOD; COORDINATE SYSTEM AB Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer - a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences. (C) 2012 Elsevier Inc. All rights reserved. C1 [Bernal-Rusiel, Jorge L.; Greve, Douglas N.; Reuter, Martin; Fischl, Bruce; Sabuncu, Mert R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Fischl, Bruce; Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU Alzheimer's Disease Neuroimaging Initiative (ADNI); National Institutes of Health (NIH) [U01 AG024904]; National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering; National Center for Research Resources [P41-RR14075]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG022381]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 N5052585-01, 1R21NS072652-01, 1R01NS070963, 2R01NS042861-06A1, 5P01NS058793-03]; National Institute of Child Health and Human Development [R01-HD071664]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project; Ellison Medical Foundation; NIH [5R01AG008122-22]; NIH Blueprint for Neuroscience Research, part of the multi-institutional Human Connectome Project [5U01-MH093765]; KL2 Medical Research Investigator Training (MeRIT) grant awarded via Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [1KL2RR025757-01]; Harvard University; AHAF Alzheimer's Disease pilot grant [AHAF A2012333]; NIH K25 grant [NIBIB 1K25EB013649-01] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the National Institutes of Health (NIH) (grant U01 AG024904). The ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott Laboratories, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation Plc, Genentech Inc, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson Services Inc, Eli Lilly and Company, Medpace Inc, Merck and Co Inc, Novartis International AG, Pfizer Inc, F. Hoffman-La Roche Ltd, Schering-Plough Corporation, CCBR-SYNARC Inc, and Wyeth Pharmaceuticals, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to the ADNI are facilitated by the Foundation for the NIH. The grantee organization is the Northern California Institute for Research and Education Inc, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The ADNI data are disseminated by the Laboratory for NeuroImaging at the University of California, Los Angeles.; Support for this research was provided in part by the National Center for Research Resources (P41-RR14075), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 N5052585-01, 1R21NS072652-01, 1R01NS070963, 2R01NS042861-06A1, 5P01NS058793-03), the National Institute of Child Health and Human Development (R01-HD071664), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, by the NIH 5R01AG008122-22 grant, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. Dr. Sabuncu received support from a KL2 Medical Research Investigator Training (MeRIT) grant awarded via Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH grant #1KL2RR025757-01 and financial contributions from Harvard University and its affiliated academic health care centers), an AHAF Alzheimer's Disease pilot grant (AHAF A2012333), and an NIH K25 grant (NIBIB 1K25EB013649-01). NR 76 TC 51 Z9 51 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2013 VL 66 BP 249 EP 260 DI 10.1016/j.neuroimage.2012.10.065 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 190QR UT WOS:000322355800027 PM 23123680 ER PT J AU Zhu, Q Nelissen, K Van den Stock, J De Winter, FL Pauwels, K de Gelder, B Vanduffel, W Vandenbulcke, M AF Zhu, Qi Nelissen, Koen Van den Stock, Jan De Winter, Francois-Laurent Pauwels, Karl de Gelder, Beatrice Vanduffel, Wim Vandenbulcke, Mathieu TI Dissimilar processing of emotional facial expressions in human and monkey temporal cortex SO NEUROIMAGE LA English DT Article DE fMRI; Emotions; Facial expressions; Monkey; Human; STS ID CORTICAL AREAS TE; VISUAL-CORTEX; HUMAN BRAIN; NEURAL REPRESENTATIONS; SELECTIVE RESPONSES; SOCIAL-PERCEPTION; RHESUS MACAQUES; CONTRAST AGENT; FACE PATCH; FMRI AB Emotional facial expressions play an important role in social communication across primates. Despite major progress made in our understanding of categorical information processing such as for objects and faces, little is known, however, about how the primate brain evolved to process emotional cues. In this study, we used functional magnetic resonance imaging (fMRI) to compare the processing of emotional facial expressions between monkeys and humans. We used a 2 x 2 x 2 factorial design with species (human and monkey), expression (fear and chewing) and configuration (intact versus scrambled) as factors. At the whole brain level, neural responses to conspecific emotional expressions were anatomically confined to the superior temporal sulcus (STS) in humans. Within the human STS, we found functional subdivisions with a face-selective right posterior STS area that also responded to emotional expressions of other species and a more anterior area in the right middle STS that responded specifically to human emotions. Hence, we argue that the latter region does not show a mere emotion-dependent modulation of activity but is primarily driven by human emotional facial expressions. Conversely, in monkeys, emotional responses appeared in earlier visual cortex and outside face-selective regions in inferior temporal cortex that responded also to multiple visual categories. Within monkey IT, we also found areas that were more responsive to conspecific than to non-conspecific emotional expressions but these responses were not as specific as in human middle STS. Overall, our results indicate that human STS may have developed unique properties to deal with social cues such as emotional expressions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zhu, Qi; Nelissen, Koen; Pauwels, Karl; Vanduffel, Wim] Katholieke Univ Leuven, Lab Neuro & Psychophysiol, Louvain, Belgium. [Nelissen, Koen; de Gelder, Beatrice; Vanduffel, Wim] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [Van den Stock, Jan; De Winter, Francois-Laurent; de Gelder, Beatrice; Vandenbulcke, Mathieu] Katholieke Univ Leuven, Dept Neurosci, Div Psychiat, BELL, Louvain, Belgium. RP Vanduffel, W (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA. EM wim@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014; Pauwels, Karl/B-1074-2013 OI Van den Stock, Jan/0000-0001-5756-3195; Pauwels, Karl/0000-0003-3731-0582 FU Fund for Scientific Research (Flanders) [G.0746.09, G.0622.08, G.0831.11]; Hercules II funding; Inter University Attraction Pole [6/29]; National Institute of Neurological Disorders and Stroke [R21NS064432]; National Science Foundation in the USA [BCS-0745436]; Geconcerteerde Onderzoeks Actie [10/19]; [PFV/10/008] FX We thank C. Fransen, C. Van Eupen and A. Coeman for animal training and care; H. Kolster, W. Depuydt G. Meulemans, P. Kayenbergh, M. De Paep, S. Verstraeten, M. Docx, and I. Puttemans for technical assistance. In addition, we thank I. Popivanov, R. Vogels, J. Jastorff and N. Caspari for their help with the localizer experiment. This work was supported by the Fund for Scientific Research (Flanders) G.0746.09, G.0622.08, and G.0831.11, Hercules II funding, Inter University Attraction Pole 6/29, the National Institute of Neurological Disorders and Stroke (R21NS064432), and the National Science Foundation (BCS-0745436) in the USA, Programme Financing PFV/10/008, and Geconcerteerde Onderzoeks Actie 10/19. Q.Z., K.N. and J.V.d.S. are postdoctoral fellows of the FWO Vlaanderen. NR 77 TC 10 Z9 10 U1 5 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2013 VL 66 BP 402 EP 411 DI 10.1016/j.neuroimage.2012.10.083 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 190QR UT WOS:000322355800043 PM 23142071 ER PT J AU Carmichael, O McLaren, DG Tommet, D Mungas, D Jones, RN AF Carmichael, Owen McLaren, Donald G. Tommet, Douglas Mungas, Dan Jones, Richard N. CA Alzheimer's Dis Neuroimaging Initi TI Coevolution of brain structures in amnestic mild cognitive impairment SO NEUROIMAGE LA English DT Article DE MRI parcellation; Longitudinal cortical change; Alzheimer's disease; Exploratory factor analysis; Distributed networks ID HUMAN CEREBRAL-CORTEX; NEUROIMAGING INITIATIVE ADNI; MAGNETIC-RESONANCE IMAGES; MIDLIFE BLOOD-PRESSURE; SURFACE-BASED ANALYSIS; DEFAULT-MODE NETWORK; ALZHEIMERS-DISEASE; COORDINATE SYSTEM; CORTICAL SURFACE; INDIVIDUAL-DIFFERENCES AB Network accounts of the progression of Alzheimer's disease (AD), based on cross-sectional brain imaging observations, postulate that the biological course of the disease is characterized by coordinated spatial patterns of brain change to distributed cognitive networks. This study tests this conjecture by quantifying inter-regional covariance in cortical gray matter atrophy rates in 317 Alzheimer's Disease Neuroimaging Initiative participants who were clinically diagnosed with amnestic mild cognitive impairment at baseline and underwent serial MRI at 6-month intervals over the course of 2 years. A factor analysis model identified five factors (i.e. groupings of regions) that exhibited highly correlated rates of atrophy. Four groupings approximately corresponded to coordinated change within the posterior default mode network, prefrontal cortex, medial temporal lobe, and regions largely spared by the early pathological course of AD (i.e., sensorimotor and occipital cortex), while the fifth grouping represented diffuse, global atrophy. The data-driven observation of "frontal aging" superimposed upon medial temporal atrophy typical of early AD and default mode network changes supports the view that in individuals at high risk of eventual clinical AD, multiple patterns of distributed neuronal death corresponding to multiple biological substrates may be active. (C) 2012 Elsevier Inc. All rights reserved. C1 [Carmichael, Owen; Mungas, Dan] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [McLaren, Donald G.] ENRM Vet Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [McLaren, Donald G.] Harvard Univ, Sch Med, Boston, MA USA. [Tommet, Douglas; Jones, Richard N.] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA. [Jones, Richard N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Carmichael, O (reprint author), Ctr Neurosci, 1544 Newton Court, Davis, CA 95618 USA. EM ocarmichael@ucdavis.edu; mclaren@nmr.mgh.harvard.edu; DougTommet@hsl.harvard.edu; jones@hsl.harvard.edu RI Jones, Richard/J-3488-2013; OI Jones, Richard/0000-0002-1049-218X; McLaren, Donald/0000-0002-0566-4610 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; National Institutes of Health [AG010129, AG030514, AG030995, AG036694, AG027171]; Edward Fein Foundation (Nevada) FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by National Institutes of Health grants AG010129, AG030514, AG030995, AG036694, and AG027171. Drs. Jones was supported in part by the Edward Fein Foundation (Nevada) and through the generosity of Vicki and Arthur Loring (Massachusetts). The contents do not represent the views of the Dept. of Veterans Affairs, the United States Government, or any other funding entities. NR 64 TC 5 Z9 5 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2013 VL 66 BP 449 EP 456 DI 10.1016/j.neuroimage.2012.10.029 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 190QR UT WOS:000322355800047 PM 23103689 ER PT J AU Brown, K Xie, S Qiu, XL Mohrin, M Shin, JY Liu, YF Zhang, D Scadden, DT Chen, D AF Brown, Katharine Xie, Stephanie Qiu, Xiaolei Mohrin, Mary Shin, Jiyung Liu, Yufei Zhang, Dan Scadden, David T. Chen, Danica TI SIRT3 Reverses Aging-Associated Degeneration SO CELL REPORTS LA English DT Article ID HEMATOPOIETIC STEM-CELLS; REGULATES LIFE-SPAN; OXIDATIVE STRESS; HOMEOSTASIS; DEACETYLATION; MITOCHONDRIA; RESTRICTION; ACETYLATION; PATHWAYS; SIRTUINS AB Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin. C1 [Brown, Katharine; Qiu, Xiaolei; Mohrin, Mary; Shin, Jiyung; Zhang, Dan; Chen, Danica] Univ Calif Berkeley, Program Metab Biol Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Liu, Yufei] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Xie, Stephanie; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr, Boston, MA 02114 USA. [Xie, Stephanie; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu; danicac@berkeley.edu FU Searle Scholars Program; Hellman Family Faculty Funds; Ellison Medical Foundation; NIH [R01AG040990]; UCOP TRDRP; American Heart Association; Siebel Stem Cell Institute; CIRM; NSF FX We thank F. Alt and H. Cheng for reagents. This work was supported by Searle Scholars Program (to D.C.), the Hellman Family Faculty Funds (to D.C.), the Ellison Medical Foundation (to D.C.), the NIH (R01AG040990; to D.C.), UCOP TRDRP (to D.C.), American Heart Association (to D.C.), the Siebel Stem Cell Institute (to D.C., X.Q., and M.M.), the CIRM (to X.Q.), and the NSF (to J.S.). NR 26 TC 86 Z9 91 U1 3 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD FEB PY 2013 VL 3 IS 2 BP 319 EP 327 DI 10.1016/j.celrep.2013.01.005 PG 9 WC Cell Biology SC Cell Biology GA 184MS UT WOS:000321895200007 PM 23375372 ER PT J AU El Ouaamari, A Kawamori, D Dirice, E Liew, CW Shadrach, JL Hu, J Katsuta, H Hollister-Lock, J Qian, WJ Wagers, AJ Kulkarni, RN AF El Ouaamari, Abdelfattah Kawamori, Dan Dirice, Ercument Liew, Chong Wee Shadrach, Jennifer L. Hu, Jiang Katsuta, Hitoshi Hollister-Lock, Jennifer Qian, Wei-Jun Wagers, Amy J. Kulkarni, Rohit N. TI Liver-Derived Systemic Factors Drive beta Cell Hyperplasia in Insulin-Resistant States SO CELL REPORTS LA English DT Article ID GROWTH-FACTOR; COMPENSATORY GROWTH; GLUCOSE-INTOLERANCE; RECEPTOR; PROLIFERATION; MICE; MASS; ACTIVATION; EXPANSION; PANCREAS AB Integrative organ crosstalk regulates key aspects of energy homeostasis, and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that crosstalk between the liver and pancreatic islets modulates beta cell growth in response to insulin resistance, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, as well as in vitro islet culture approaches, we demonstrate that humoral, nonneural, non-cell-autonomous factor(s) induces beta cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human beta cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of beta cell growth factor(s) in insulin-resistant states. C1 [El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Wagers, Amy J.; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. [Katsuta, Hitoshi; Hollister-Lock, Jennifer] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Katsuta, Hitoshi; Hollister-Lock, Jennifer] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Qian, Wei-Jun] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. EM rohit.kulkarni@joslin.harvard.edu RI Dirice, Ercument/B-2825-2017 FU NIH [RO1 DK 067536]; Societe Francophone du Diabete; Association Francaise des Diabetiques; American Diabetes Association; Burroughs Wellcome Fund [NIH 5 P30 DK36836-20, NIH 1 DP2 OD004345]; Harvard Stem Cell Institute Seed Grant; Juvenile Diabetes Research Foundation/Sanofi Aventis Strategic Alliance [17-2011-644]; [R01 DK 074795] FX We are grateful to C. Ronald Kahn for sharing the LIRKO model. We thank the laboratory of Gordon Weir for assistance in transplantation experiments, T. Roderick Bronson for assistance with histology, and Amarnath Kurpad, Marta Robledo, Samantha Haring, Rachael Martinez, and Ben Hambro for technical assistance. This work is supported by NIH RO1 DK 067536 (to R.N.K.); Societe Francophone du Diabete, Association Francaise des Diabetiques, and American Diabetes Association (to A.E.O.); R01 DK 074795 (to W.-J.Q.); and the Burroughs Wellcome Fund, NIH 5 P30 DK36836-20, and NIH 1 DP2 OD004345 (to A.J.W.). A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Part of the study was supported by a Harvard Stem Cell Institute Seed Grant (to R.N.K.) and by a grant from the Juvenile Diabetes Research Foundation/Sanofi Aventis Strategic Alliance (17-2011-644) (to R.N.K.). NR 40 TC 51 Z9 52 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD FEB PY 2013 VL 3 IS 2 BP 401 EP 410 DI 10.1016/j.celrep.2013.01.007 PG 10 WC Cell Biology SC Cell Biology GA 184MS UT WOS:000321895200015 PM 23375376 ER PT J AU Price, M Davidson, TM Andrews, JO Ruggiero, KJ AF Price, Matthew Davidson, Tatiana M. Andrews, Jeannette O. Ruggiero, Kenneth J. TI Access, use and completion of a brief disaster mental health intervention among Hispanics, African-Americans and Whites affected by Hurricane Ike SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID RECRUITMENT AB African-Americans and Hispanics are disproportionally affected by disasters. We evaluated differences in the use and completion of a web-based mental health intervention, Disaster Recovery Web (DRW), by White, African-American and Hispanic adults in the aftermath of Hurricane Ike. Approximately one year after the hurricane, a telephone survey was carried out with adults from Galveston and Chambers counties. A total of 1249 adults participated in the survey (80% White, 14% African-American and 6% Hispanic). Mental health and mental health service utilization were assessed. Whites were more likely to have previously used the Internet to obtain general health information than African-Americans or Hispanics (P < 0.001). A logistic regression was used to identify differences in the use of the Internet intervention after controlling for covariates. There were no differences in rates of non-use and dropout attrition between Whites, African-Americans and Hispanics. Thus the findings suggest that web-based mental health interventions can be used to reach African-American, Hispanic and White adults at similar rates after a disaster. C1 [Price, Matthew; Davidson, Tatiana M.; Andrews, Jeannette O.; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Price, M (reprint author), Natl Crime Victims Res & Treatment Ctr, 67 President St,2 South MSC 861, Charleston, SC 29425 USA. EM prima@musc.edu FU National Institute of Mental Health [R34 MH77149, R01 MH081056-03S2]; South Carolina Clinical and Translational Research Institute [NCRR/NIH UL1 RR029882]; [T32 MH018869]; [P60 MH082598] FX The study was supported by National Institute of Mental Health grant R34 MH77149. Dr Price was supported by T32 MH018869. Dr Davidson was supported by National Institute of Mental Health grant R01 MH081056-03S2. Dr Ruggiero was supported by P60 MH082598. Dr Andrews was supported by the South Carolina Clinical and Translational Research Institute (NCRR/NIH UL1 RR029882). NR 17 TC 8 Z9 8 U1 1 U2 6 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PD FEB PY 2013 VL 19 IS 2 BP 70 EP 74 DI 10.1177/1357633X13476230 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 184OO UT WOS:000321901300002 PM 23514936 ER PT J AU Magnani, JW Wang, N Nelson, KP Connelly, S Deo, R Rodondi, N Schelbert, EB Garcia, ME Phillips, CL Shlipak, MG Harris, TB Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Wang, Na Nelson, Kerrie P. Connelly, Stephanie Deo, Rajat Rodondi, Nicolas Schelbert, Erik B. Garcia, Melissa E. Phillips, Caroline L. Shlipak, Michael G. Harris, Tamara B. Ellinor, Patrick T. Benjamin, Emelia J. CA Hlth Aging Body Composition Study TI Electrocardiographic PR Interval and Adverse Outcomes in Older Adults The Health, Aging, and Body Composition Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ECG; epidemiology; heart failure; risk factors ID CONGESTIVE-HEART-FAILURE; MIDDLE-AGED MEN; ATRIAL-FIBRILLATION; METABOLIC SYNDROME; ATHEROSCLEROSIS RISK; ATRIOVENTRICULAR-BLOCK; CARDIOVASCULAR-DISEASE; COMMUNITIES; OBESITY; SCORE AB Background- The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. Methods and Results- The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74 +/- 3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality. Conclusions- We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women. C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Cardiol Sect,Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 02118 USA. [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Nelson, Kerrie P.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Connelly, Stephanie] Univ Tennessee, Dept Med, Memphis, TN 38104 USA. [Deo, Rajat] Univ Penn, Div Cardiovasc Med, Sect Electrophysiol, Philadelphia, PA 19104 USA. [Rodondi, Nicolas] Univ Bern, Dept Gen Internal Med, Bern, Switzerland. [Schelbert, Erik B.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA. [Garcia, Melissa E.; Phillips, Caroline L.; Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown & Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging; American Heart Association Award [09FTF2190028]; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA grant [R01-AG028050]; National Institute of Nursing Research grant [R01-NR012459]; National Institutes of Health [1RC1HL101056, 1RO1HL092577, 5R21DA027021, 1RO1HL104156, 1K24HL105780, K23DK089118] FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.; This research was funded by American Heart Association Award 09FTF2190028 (J.W.M.); by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; National Institute of Nursing Research grant R01-NR012459, and by National Institutes of Health grants 1RC1HL101056 (E.J.B.), 1RO1HL092577 (E.J.B. and P.T.E.), 5R21DA027021, 1RO1HL104156, 1K24HL105780 (P.T.E.), and K23DK089118 (R.D.). NR 31 TC 32 Z9 33 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2013 VL 6 IS 1 BP 84 EP 90 DI 10.1161/CIRCEP.112.975342 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167YE UT WOS:000320670700016 PM 23243193 ER PT J AU Lakdawala, NK Winterfield, JR Funke, BH AF Lakdawala, Neal K. Winterfield, Jeffery R. Funke, Birgit H. TI Dilated Cardiomyopathy SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE arrhythmia (heart rhythm disorders); cardiomyopathy, dilated; genetics; heart failure ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LAMIN A/C GENE; CARDIAC-RESYNCHRONIZATION THERAPY; SENSORINEURAL HEARING-LOSS; MUSCULAR-DYSTROPHY; MAGNETIC-RESONANCE; PRIMARY PREVENTION; SUDDEN-DEATH; VENTRICULAR-ARRHYTHMIAS; ATRIOVENTRICULAR-BLOCK C1 [Lakdawala, Neal K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lakdawala, Neal K.] Harvard Univ, Sch Med, Boston VA Hosp, Boston, MA USA. [Winterfield, Jeffery R.] Loyola Univ, Med Ctr, Cardiovasc Inst, Maywood, IL 60153 USA. [Funke, Birgit H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Healthcare Ctr Personalized Genet Med,De, Boston, MA USA. RP Lakdawala, NK (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM nlakdawala@partners.org FU NHLBI NIH HHS [U01 HL084877] NR 88 TC 22 Z9 27 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2013 VL 6 IS 1 BP 228 EP 237 DI 10.1161/CIRCEP.111.962050 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167YE UT WOS:000320670700033 PM 23022708 ER PT J AU Chen, CC Kasper, EM Zinn, PO Warnke, PC AF Chen, Clark C. Kasper, Ekkehard M. Zinn, Pascal O. Warnke, Peter C. TI Management of Entrapped Temporal Horn by Temporal Horn to Prepontine Cistern Shunting SO WORLD NEUROSURGERY LA English DT Article DE Entrapped temporal horn; Prepontine cistern; Shunting ID HYDROCEPHALUS; ENTRAPMENT AB BACKGROUND: Entrapped temporal horn syndrome secondary to obstructive neoplastic lesions is most frequently treated by surgical excision of the offending lesion. Here we describe an alternate approach involving temporal horn to prepontine cistern shunting followed by radiosurgery of the offending lesion. METHODS: A 41-year-old woman with a history of meningiomatosis presented with progressive, incapacitating headache. Magnetic resonance imaging (MRI) showed growth of a right trigone meningioma, causing entrapment of the right temporal horn. A ventricular catheter was placed using frame-based stereotaxy and image fusion computed tomography/MRI to connect the entrapped lateral ventricle to the prepontine cistern. The patient reported complete resolution of her symptoms after the procedure. RESULTS: Postoperative MRI revealed decompression of the temporal horn. The trigonal meningioma was treated with stereotactic radiosurgery. The patient remained asymptomatic at the 2-year follow-up. CONCLUSIONS: Trapped temporal horn syndrome secondary to obstructive neoplastic lesions can be treated by internal shunting followed by radiosurgery. C1 [Chen, Clark C.; Kasper, Ekkehard M.; Zinn, Pascal O.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Neurosurg, Boston, MA 02215 USA. [Chen, Clark C.; Zinn, Pascal O.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Warnke, Peter C.] Univ Chicago, Neurosurg Sect, Chicago, IL 60637 USA. RP Chen, CC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Neurosurg, Boston, MA 02215 USA. EM cchen1@partners.org NR 13 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 J9 WORLD NEUROSURG JI World Neurosurg. PD FEB PY 2013 VL 79 IS 2 AR 404.e7 DI 10.1016/j.wneu.2011.02.025 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 165VL UT WOS:000320513600002 PM 22120406 ER PT J AU Kapoor, R Piris, A Saavedra, AP Duncan, LM Nazarian, RM AF Kapoor, Roger Piris, Adriano Saavedra, Arturo P. Duncan, Lyn M. Nazarian, Rosalynn M. TI Wolf Isotopic Response Manifesting as Postherpetic Granuloma Annulare A Case Series SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HEALED HERPES-ZOSTER; OF-THE-LITERATURE; LICHEN-PLANUS; CUTANEOUS REACTIONS; SITE; INFECTION; VASCULITIS; KOEBNER; SCARS AB Context.-Wolf isotopic response has infrequently been reported in the literature, mainly as isolated case reports. Objective.-To aid in recognition of the occurrence of postherpetic granuloma annulare for accurate histologic interpretation of granulomatous dermatitides. Design.-We report 5 cases of patients with Wolf isotopic response manifesting as granuloma annulare, developing in a site of previous herpes zoster, and discuss the clinicopathologic findings. Results.-Previous infection with herpes zoster or herpes simplex virus was found in 5 of 5 cases reported. The differential diagnosis of a dermal lymphohistiocytic infiltrate with multinucleated giant cells includes postherpetic granuloma annulare. Conclusions.-All cases of postherpetic Wolf isotopic response reported in this series revealed granuloma annulare, with a perineurovascular or perifollicular pattern of lymphohistiocytic infiltration including multinucleated giant cells, and occurred following herpes zoster or herpes simplex infection, although herpes viral infection was not always associated with a subsequent isotopic eruption. Awareness of this entity can aid in the clinicopathologic diagnosis of granuloma annulare occurring at the site of prior herpes viral infection. C1 [Kapoor, Roger; Nazarian, Rosalynn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Piris, Adriano; Duncan, Lyn M.; Nazarian, Rosalynn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit,Pathol Serv, Boston, MA 02114 USA. [Saavedra, Arturo P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol & Pathol, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 50 Staniford St,Suite 200, Boston, MA 02114 USA. EM rmnazarian@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 22 TC 10 Z9 10 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2013 VL 137 IS 2 BP 255 EP 258 DI 10.5858/arpa.2011-0643-OA PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 155VH UT WOS:000319776000017 PM 23368868 ER PT J AU Kong, JY Hou, JB Ma, LJ Xing, L Jia, HB Liu, HM Zhang, SS Yu, B Jang, IK AF Kong, Junying Hou, Jingbo Ma, Lijia Xing, Lei Jia, Haibo Liu, Huimin Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Cutting balloon combined with paclitaxel-eluting balloon for treatment of in-stent restenosis SO ARCHIVES OF CARDIOVASCULAR DISEASES LA English DT Article DE In-stent restenosis; Angioplasty; Animal model; Apoptosis ID LASER CORONARY ANGIOPLASTY; LONG-TERM OUTCOMES; ROTATIONAL ATHERECTOMY; RADIATION-THERAPY; ARTERY INJURY; FOLLOW-UP; TRIAL; INTERVENTIONS; IMPLANTATION; MECHANISMS AB Background. - The optimal therapy for in-stent restenosis (ISR) is controversial. We evaluated three different strategies for the treatment of in-stent restenosis: cutting balloon angioplasty (CBA), paclitaxel-eluting balloon angioplasty (PEBA) and cutting balloon followed by paclitaxel-eluting balloon angioplasty (CB + PEBA). Methods. - Forty-five coronary arteries in 45 mini-pigs underwent oversized bare-metal stent (stent-to-artery ratio, 1.2:1) implantation to induce in-stent restenosis. After 28 days, vessels with in-stent restenosis (>= 50% diameter stenosis) were randomly divided into three groups: CBA, PEBA and CB + PEBA. In vivo angiography was performed before intervention, immediately after intervention and at 28-day follow-up. Stented arteries were harvested for pathological analyses. The proliferation and apoptosis of vascular smooth muscle cells were evaluated by imunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, respectively. Results. - Acute lumen gain was not different between the three groups. Late lumen loss and neointimal area at follow-up were lower for CB + PEBA compared with CBA but similar for CB + PEBA compared with PEBA. There were no significant differences in proliferating cell nuclear antigen-positive vascular smooth muscle cells and TUNEL-positive vascular smooth muscle cells between the CB + PEBA and PEBA groups. Conclusions. - PEBA with or without cutting balloon was superior to CBA alone for in-stent restenosis. The underlying mechanism was probably related to inhibition of smooth muscle cell proliferation and increased apoptosis. In this porcine coronary artery restenosis model, PEBA with or without cutting balloon was superior. (c) 2013 Elsevier Masson SAS. All rights reserved. C1 [Kong, Junying; Hou, Jingbo; Ma, Lijia; Xing, Lei; Jia, Haibo; Liu, Huimin; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Minist Myocardial Ischaemia Mech & Treatment, Dept Cardiol,Key Labs Educ, Harbin 150086, Heilongjiang, Peoples R China. [Zhang, Shaosong] St Jude Med, LightLab Imaging, Westford, MA USA. [Zhang, Shaosong] Harbin Med Univ, Harbin 150086, Heilongjiang, Peoples R China. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Minist Myocardial Ischaemia Mech & Treatment, Dept Cardiol,Key Labs Educ, Harbin 150086, Heilongjiang, Peoples R China. EM yuboteacher@163.com NR 28 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1875-2136 J9 ARCH CARDIOVASC DIS JI Arch. Cardiovasc. Dis. PD FEB PY 2013 VL 106 IS 2 BP 79 EP 85 DI 10.1016/j.acvd.2012.10.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141WL UT WOS:000318757100003 PM 23527911 ER PT J AU Laden, F Chiu, YH Garshick, E Hammond, SK Hart, JE AF Laden, Francine Chiu, Yueh-Hsiu Garshick, Eric Hammond, S. Katharine Hart, Jaime E. TI A cross-sectional study of secondhand smoke exposure and respiratory symptoms in non-current smokers in the US trucking industry: SHS exposure and respiratory symptoms SO BMC PUBLIC HEALTH LA English DT Article DE Occupational health; Secondhand smoke; Respiratory symptoms ID ENVIRONMENTAL TOBACCO-SMOKE; PASSIVE SMOKING; LUNG-FUNCTION; BRONCHIAL RESPONSIVENESS; CHRONIC RHINOSINUSITIS; GENERAL-POPULATION; CIGARETTE-SMOKING; 2ND-HAND SMOKE; HEALTH SURVEY; WOMEN AB Background: Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Methods: Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. Results: In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose-response, except for chronic phlegm. Conclusions: In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms. C1 [Laden, Francine; Chiu, Yueh-Hsiu; Hart, Jaime E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Laden, Francine; Garshick, Eric; Hart, Jaime E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Laden, Francine; Garshick, Eric; Hart, Jaime E.] Harvard Univ, Sch Med, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA. RP Laden, F (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM francine.laden@channing.harvard.edu FU Flight Attendants Medical Research Institute (FAMRI) Young Investigators Award; NIH/NCI [R01 CA90792] FX This study was supported by the Flight Attendants Medical Research Institute (FAMRI) Young Investigators Award and NIH/NCI R01 CA90792. NR 40 TC 1 Z9 2 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD FEB 1 PY 2013 VL 13 AR 93 DI 10.1186/1471-2458-13-93 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 145WN UT WOS:000319050100001 PM 23368999 ER PT J AU Kraybill, ML Thorgusen, SR Suchy, Y AF Kraybill, Matthew L. Thorgusen, Sommer R. Suchy, Yana TI The Push-Turn-Taptap Task Outperforms Measures of Executive Functioning in Predicting Declines in Functionality: Evidence-Based Approach to Test Validation SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Executive functioning; Motor programming; Functional independence; Geriatrics; Evidence-based practice ID BEHAVIORAL DYSCONTROL SCALE; MILD COGNITIVE IMPAIRMENT; LOWER-EXTREMITY FUNCTION; DEMENTIA RATING-SCALE; ADULT AGE-DIFFERENCES; INSTRUMENTAL ACTIVITIES; OLDER-ADULTS; ECOLOGICAL VALIDITY; ELECTRONIC VERSION; ALZHEIMERS-DISEASE AB Performance on the Push-Turn-Taptap (PTT) task has been shown to be a strong predictor of concurrent everyday functioning. This study utilized a prospective, longitudinal design to evaluate the PTT task for predicting future performance on a behavioral assessment of everyday functioning. The PTT task was compared to other measures of executive functioning as well as general cognition in terms of administration time and ability to identify participants who evidenced functional decline. A total of 50 community-dwelling older adults (ages 5887) completed the PTT task, Mattis Dementia Rating Scale, Geriatric Depression Scale, Behavioral Dyscontrol Scale, Delis-Kaplan Executive Function System, and Timed Instrumental Activities of Daily Living. Baseline PTT performance (a) was highly correlated with an objective measure of everyday functioning after approximately one year (r=.497, p<.001), (b) was associated with changes in follow-up functioning, F(3, 46)=3.15, p=.03, (c) was a better predictor of future functional status than a longer battery of EF, and (d) reliably identified individuals with the greatest magnitude of functional decline. The PTT tasks may provide a particularly advantageous method of predicting future changes in everyday functioning in older adults. C1 [Kraybill, Matthew L.; Thorgusen, Sommer R.; Suchy, Yana] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. RP Kraybill, ML (reprint author), San Francisco VA Med Ctr, 4150 Clement St,S-116, San Francisco, CA 94121 USA. EM mkraybill@gmail.com OI Suchy, Yana/0000-0001-6513-565X NR 73 TC 8 Z9 8 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD FEB 1 PY 2013 VL 27 IS 2 BP 238 EP 255 DI 10.1080/13854046.2012.735702 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 146MH UT WOS:000319094700004 PM 23116212 ER PT J AU Choi, YJ Sicinski, P AF Choi, Yoon Jong Sicinski, Piotr TI Unexpected Outcomes of CDK4/6 Inhibition SO ONCOTARGET LA English DT Editorial Material ID CYCLIN D; THERAPY; CANCER C1 [Choi, Yoon Jong; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Choi, Yoon Jong; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA083688] NR 10 TC 6 Z9 6 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD FEB PY 2013 VL 4 IS 2 BP 176 EP 177 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 142FO UT WOS:000318782500002 PM 23563596 ER PT J AU Falchook, GS Trent, JC Heinrich, MC Beadling, C Patterson, J Bastida, CC Blackman, SC Kurzrock, R AF Falchook, G. S. Trent, J. C. Heinrich, M. C. Beadling, C. Patterson, J. Bastida, C. C. Blackman, S. C. Kurzrock, R. TI BRAF Mutant Gastrointestinal Stromal Tumor: First report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance SO ONCOTARGET LA English DT Article DE Gastrointestinal stromal tumor; Dabrafenib; GSK2118436; BRAF mutation; BRAF inhibition; V600E ID IMATINIB MESYLATE; PHASE-II; MUTATIONS; MELANOMA; GENE; CANCER; PDGFRA; GIST AB Activating oncogenic mutations of BRAF have been described in patients with gastrointestinal stromal tumor (GIST), but treatment of GIST with BRAF inhibitors and mechanisms of mediating the emergence of resistance in GIST have not been reported. Dabrafenib is a potent ATP-competitive inhibitor of BRAF kinase and is highly selective for mutant BRAF in kinase panel screening, cell lines, and xenografts. We report prolonged antitumor activity in the first patient with V600E BRAF-mutated GIST who was treated with a BRAF inhibitor. Whole exome sequencing performed in tumor tissue obtained at the time of progressive disease demonstrated a somatic gain-of-function PIK3CA mutation (H1047R) as well as a CDKN2A aberration, which may have contributed to eventual resistance to treatment. C1 [Falchook, G. S.; Bastida, C. C.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA. [Trent, J. C.] Univ Miami, Sarcoma Med Oncol Program, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Heinrich, M. C.; Beadling, C.; Patterson, J.] Portland VA Med Ctr, Portland, OR USA. [Heinrich, M. C.; Beadling, C.; Patterson, J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Oncol, Portland, OR 97201 USA. [Blackman, S. C.] GlaxoSmithKline, Collegeville, PA USA. [Kurzrock, R.] Univ Calif San Diego, Dept Med, Hematol Oncol Div, Moores Canc Ctr, San Diego, CA 92103 USA. RP Falchook, GS (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA. EM gfalchoo@mdanderson.org FU Center for Clinical and Translational Sciences; National Institutes of Health Clinical and Translational Science Award [UL1 RR024148]; National Institutes of Health Cancer Center Support Grant (CCSG) [CA016672]; GIST Cancer Research Fund; Life Raft Group; VA Merit Review Grant; GlaxoSmithKline; Novartis; Pfizer FX This work was performed in the U.T. MD Anderson Cancer Center Clinical and Translational Research Center (CTRC) and was supported by the Center for Clinical and Translational Sciences, which is funded by National Institutes of Health Clinical and Translational Science Award UL1 RR024148 and by the National Institutes of Health Cancer Center Support Grant (CCSG) award CA016672 to MD Anderson Cancer Center. Short read sequencing assays were performed by the Oregon Health & Science University Massively Parallel Sequencing Shared Resource. Funded in part by philanthropic donations from the GIST Cancer Research Fund and the Life Raft Group (MCH) and a VA Merit Review Grant (MCH). We would like to thank Dr. Vicki Goodman of GlaxoSmithKline for her comments on this manuscript.; Gerald Falchook received research funding and travel reimbursement for conference attendance from GlaxoSmithKline. Razelle Kurzrock received research funding from GlaxoSmithKline, Novartis, and Pfizer. Samuel Blackman was an employee of GlaxoSmithKline at the time of the study. The other coauthors report no conflicts of interest. NR 25 TC 40 Z9 41 U1 0 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD FEB PY 2013 VL 4 IS 2 BP 310 EP 315 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 142FO UT WOS:000318782500017 PM 23470635 ER PT J AU Yamanaka, YJ Gierahn, TM Love, JC AF Yamanaka, Yvonne J. Gierahn, Todd M. Love, J. Christopher TI The dynamic lives of T cells: new approaches and themes SO TRENDS IN IMMUNOLOGY LA English DT Review DE T cells; dynamics; heterogeneity; multiparameter measurements; single-cell analysis ID IN-VIVO REVEALS; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSES; SINGLE-CELL; CUTTING EDGE; LYMPH-NODES; HISTONE ACETYLATION; FLOW-CYTOMETRY; TH2 CELLS; ANTIGEN PRESENTATION AB Activated T cells have classically been thought to progress unidirectionally through discrete phenotypic states and differentiate into static lineages. It is increasingly evident, however, that T cells exhibit much more,complex and flexible dynamic behaviors than initially appreciated, and that these behaviors influence the efficacy of T cell responses to immunological challenges. In this review, we discuss how new technologies for monitoring the dynamics of T cells are enhancing the resolution of the fine phenotypic and functional heterogeneity within populations of T cells and revealing how individual T cells transition among a continuum of states. Such insights into the dynamic properties of T cells should improve immune monitoring and inform strategies for therapeutic interventions. C1 [Yamanaka, Yvonne J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Gierahn, Todd M.; Love, J. Christopher] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Love, J. Christopher] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. [Love, J. Christopher] Harvard Univ, Boston, MA 02129 USA. [Love, J. Christopher] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Love, JC (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM clove@mit.edu FU Charles A. Dana Foundation; W.M. Keck Foundation; NIH/NIAID [4U19AI089992, 5P01AI045757, UMI AI068618]; National Science Foundation; Collamore-Rogers Fellowship; Ragon Institute of MGH, MIT and Harvard FX We thank Qing Han, Rita Lucia Content, and Alexis Torres for helpful discussions and comments on the manuscript. This work was supported in part by funding from the Charles A. Dana Foundation, the W.M. Keck Foundation, and NIH/NIAID (4U19AI089992, 5P01AI045757, UMI AI068618). Y.J.Y is supported in part by a fellowship from the National Science Foundation and the Collamore-Rogers Fellowship. T.M.G. was supported in part by a postdoctoral fellowship from the Ragon Institute of MGH, MIT and Harvard. J.C.L. is a Latham Family Career Development Professor and Camille Dreyfus Teacher-Scholar. NR 95 TC 7 Z9 7 U1 2 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD FEB PY 2013 VL 34 IS 2 BP 59 EP 66 DI 10.1016/j.it.2012.10.006 PG 8 WC Immunology SC Immunology GA 145QG UT WOS:000319031300003 PM 23200626 ER PT J AU Lagares, D Kapoor, M AF Lagares, David Kapoor, Mohit TI Targeting Focal Adhesion Kinase in Fibrotic Diseases SO BIODRUGS LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; I COLLAGEN EXPRESSION; GROWTH-FACTOR BETA-1; SMOOTH MUSCLE ACTIN; MYOFIBROBLAST DIFFERENTIATION; TYROSINE PHOSPHORYLATION; TGF-BETA; CARDIAC-HYPERTROPHY; TRANSFORMING GROWTH-FACTOR-BETA-1; CELL-PROLIFERATION AB Fibrotic diseases such as idiopathic pulmonary fibrosis or scleroderma (systemic sclerosis) are chronic fibroproliferative disorders for which there are currently no effective treatments. Dysregulated normal tissue repair process is considered to cause a fibrotic response culminating in compromised organ function due to excess extracellular matrix deposition. The mechanisms underlying the pathophysiology of fibrosis are poorly understood. Recent findings suggest that focal adhesion kinase (FAK) plays a key role in development of fibrotic disorders, and it appears to be an attractive target for antifibrotic therapy. Here, we review the emerging role of FAK as a key regulator of fibrotic signaling and its potential as a future therapeutic target to counteract fibrosis. C1 [Lagares, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Pulm & Crit Care Unit, Boston, MA USA. [Kapoor, Mohit] Univ Montreal, Dept Med, Montreal, PQ H2L 4M1, Canada. RP Kapoor, M (reprint author), Univ Montreal, Dept Med, 1560 Sherbrooke St East,Pavillon DeSeve,Room Y262, Montreal, PQ H2L 4M1, Canada. EM mohit.kapoor.chum@ssss.gouv.qc.ca NR 79 TC 10 Z9 12 U1 0 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PD FEB PY 2013 VL 27 IS 1 BP 15 EP 23 DI 10.1007/s40259-012-0003-4 PG 9 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 138MH UT WOS:000318512200002 PM 23329396 ER PT J AU Aloia, TA Haynes, AB Vauthey, J Ferrone, C Crane, C Krishnan, S Wo, JY Hong, TS Yoon, SS AF Aloia, T. A. Haynes, A. B. Vauthey, J. Ferrone, C. Crane, C. Krishnan, S. Wo, J. Y. Hong, T. S. Yoon, S. S. TI Laparoscopic Placement of Biologic Spacers to Facilitate Dose Intense Radiotherapy for Unresectable Hepatic Malignancy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Aloia, T. A.; Haynes, A. B.; Vauthey, J.; Crane, C.; Krishnan, S.] UT MD Anderson Canc Ctr, Houston, TX USA. [Ferrone, C.; Wo, J. Y.; Hong, T. S.; Yoon, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S36 EP S36 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700088 ER PT J AU Carson, WE Otteson, RA Hughes, ME Neumayer, L Hwang, ES Laronga, C Breslin, T Chen, SL Khan, S Edge, SB Farrar, WB Weeks, JC AF Carson, W. E. Otteson, R. A. Hughes, M. E. Neumayer, L. Hwang, E. S. Laronga, C. Breslin, T. Chen, S. L. Khan, S. Edge, S. B. Farrar, W. B. Weeks, J. C. TI Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer: A Review of the National Comprehensive Cancer Network (NCCN) Database SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Carson, W. E.; Farrar, W. B.] Ohio State Univ, Columbus, OH 43210 USA. [Otteson, R. A.; Chen, S. L.] City Hope Natl Med Ctr, Duarte, CA USA. [Hughes, M. E.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neumayer, L.] Univ Utah HSC, Salt Lake City, UT USA. [Hwang, E. S.] Duke Univ, Durham, NC USA. [Laronga, C.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Breslin, T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Khan, S.] Northwestern Univ, Chicago, IL 60611 USA. [Edge, S. B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RI Carson, William/E-2846-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S10 EP S10 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700014 ER PT J AU Conrad, C Nedelcu, M Camerlo, A Simvathirtan, N Tanabe, KK Gayet, B AF Conrad, C. Nedelcu, M. Camerlo, A. Simvathirtan, N. Tanabe, K. K. Gayet, B. TI Single Incision Intragastric Surgery for T1a Gastric Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Conrad, C.] Dana Farber Partners CancerCare Surg Oncol Progra, Boston, MA USA. [Nedelcu, M.; Camerlo, A.; Simvathirtan, N.; Gayet, B.] Inst Mutualiste Montsouris, Paris, France. [Tanabe, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S36 EP S36 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700089 ER PT J AU Conrad, C Nedelcu, M Camerlo, A Simvathirtan, N Tanabe, KK Gayet, B AF Conrad, C. Nedelcu, M. Camerlo, A. Simvathirtan, N. Tanabe, K. K. Gayet, B. TI Thoracoscopic Access Facilitates Safe Exposure of Posterior/Superior Liver Lesions in Patients Ineligible for Laparoscopy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Conrad, C.] Dana Farber Partners CancerCare Surg Oncol Fellow, Boston, MA USA. [Nedelcu, M.; Camerlo, A.; Simvathirtan, N.; Gayet, B.] Inst Mutualiste Montsouris, Paris, France. [Tanabe, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S35 EP S36 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700087 ER PT J AU Erstad, D Feng, Y Ready, J Abraham, J Ferrone, ML Bertagnolli, MM Baldini, EH Raut, C AF Erstad, D. Feng, Y. Ready, J. Abraham, J. Ferrone, M. L. Bertagnolli, M. M. Baldini, E. H. Raut, C. TI Amputation for Extremity Sarcoma: Indications and Outcomes in the Modern Era SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Erstad, D.] Harvard Univ, Sch Med, Boston, MA USA. [Feng, Y.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ready, J.; Ferrone, M. L.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Ready, J.; Ferrone, M. L.] Dana Farber Canc Inst Hosp, Ctr Sarcoma & Bone Oncol, Boston, MA USA. [Abraham, J.] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. [Bertagnolli, M. M.; Raut, C.] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. [Bertagnolli, M. M.; Baldini, E. H.; Raut, C.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Baldini, E. H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S124 EP S124 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700365 ER PT J AU Fragomeni, RAS Cusack, JC AF Fragomeni, R. A. Salas Cusack, J. C. TI XPO1 and BRAF Inhibition Synergize and Modulate pRb, Survivin and ERK in Melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Fragomeni, R. A. Salas; Cusack, J. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S91 EP S91 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700259 ER PT J AU Greenup, RA Breslin, T Edge, SB Hughes, ME Hwang, ES Laronga, C Marcom, P Moy, B Otteson, RA Rugo, H Wilson, JL Wong, Y Weeks, JC AF Greenup, R. A. Breslin, T. Edge, S. B. Hughes, M. E. Hwang, E. S. Laronga, C. Marcom, P. Moy, B. Otteson, R. A. Rugo, H. Wilson, J. L. Wong, Y. Weeks, J. C. TI Outcomes after Mastectomy for Node-positive Breast Cancer: Comparison of Women Treated With and Without Completion Axillary Dissection at NCCN Cancer Centers SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Greenup, R. A.; Hwang, E. S.; Marcom, P.] Duke Univ, Med Ctr, Durham, NC USA. [Breslin, T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Edge, S. B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Hughes, M. E.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Laronga, C.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Moy, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Otteson, R. A.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Rugo, H.] UCSF, San Francisco, CA USA. [Wilson, J. L.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Wong, Y.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S9 EP S9 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700011 ER PT J AU Haynes, AB Aloia, TA Vauthey, J Ferrone, C Crane, C Wo, JY Hong, TS Yoon, SS AF Haynes, A. B. Aloia, T. A. Vauthey, J. Ferrone, C. Crane, C. Wo, J. Y. Hong, T. S. Yoon, S. S. TI Surgical Placement of Biological Mesh Spacers to Displace Bowel from Unresectable Liver Tumors Facilitates Safe Delivery of Dose-intense Radiation Therapy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Haynes, A. B.; Aloia, T. A.; Vauthey, J.; Crane, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ferrone, C.; Wo, J. Y.; Hong, T. S.; Yoon, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S86 EP S86 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700243 ER PT J AU Hyder, O Cosgrove, D Liapi, E Zhu, A Sofocleous, C Petre, E Neal, D Kalva, S Marsh, JW Geschwind, J Pawlik, T AF Hyder, O. Cosgrove, D. Liapi, E. Zhu, A. Sofocleous, C. Petre, E. Neal, D. Kalva, S. Marsh, J. W. Geschwind, J. Pawlik, T. TI Intra-arterial Therapy for Advanced Intrahepatic Cholangiocarcinoma - A Multi-Institutional Analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Hyder, O.; Cosgrove, D.; Liapi, E.; Geschwind, J.; Pawlik, T.] Johns Hopkins Univ, Baltimore, MD USA. [Neal, D.; Marsh, J. W.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Zhu, A.; Kalva, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sofocleous, C.; Petre, E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Liapi, Eleni/B-5195-2013 OI Liapi, Eleni/0000-0001-5864-4448 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S7 EP S7 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700006 ER PT J AU Kane, JM Zhang, Q Klimowicz, A Magliocco, A George, A Simko, J DeLaney, T Kraybill, W AF Kane, J. M. Zhang, Q. Klimowicz, A. Magliocco, A. George, A. Simko, J. DeLaney, T. Kraybill, W. TI High Risk Soft Tissue Sarcoma Biomarker Expression Patterns and Outcome Following Neoadjuvant Chemoradiation SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Kane, J. M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Zhang, Q.; George, A.; Kraybill, W.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [DeLaney, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Klimowicz, A.] Tom Baker Canc Clin, Calgary, AB, Canada. [Magliocco, A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Simko, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S28 EP S28 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700065 ER PT J AU Kwon, S Mann, GN Wu, P Drake, F Gow, K AF Kwon, S. Mann, G. N. Wu, P. Drake, F. Gow, K. TI General Surgery Resident Operative Experience in Surgical Oncology Over Two Decades SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Kwon, S.; Mann, G. N.; Drake, F.] Univ Washington, Seattle, WA 98195 USA. [Wu, P.] Vet Affairs Puget Sound, Seattle, WA USA. [Gow, K.] Seattle Childrens Hosp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S113 EP S114 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700333 ER PT J AU Merkow, RP Bilimoria, KY Tomlinson, JS Paruch, JL Stewart, A Winchester, D Ko, CY Bentrem, DJ AF Merkow, R. P. Bilimoria, K. Y. Tomlinson, J. S. Paruch, J. L. Stewart, A. Winchester, D. Ko, C. Y. Bentrem, D. J. TI Postoperative Complications Reduce Adjuvant Chemotherapy Use in Resectable Pancreatic Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Merkow, R. P.; Bilimoria, K. Y.; Paruch, J. L.; Stewart, A.; Winchester, D.; Ko, C. Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Bentrem, D. J.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Bentrem, D. J.] Northwestern Univ, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL 60611 USA. [Tomlinson, J. S.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Tomlinson, J. S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S27 EP S28 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700063 ER PT J AU Miller, CL Skolny, MN Jammallo, LS O'Toole, J Horick, N Shenouda, M Sadek, B Smith, BL Taghian, A Specht, MC AF Miller, C. L. Skolny, M. N. Jammallo, L. S. O'Toole, J. Horick, N. Shenouda, M. Sadek, B. Smith, B. L. Taghian, A. Specht, M. C. TI Risk of Lymphedema after Mastectomy - Potential Benefit of Applying Z11 Protocol to Mastectomy Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Miller, C. L.; Skolny, M. N.; Jammallo, L. S.; O'Toole, J.; Horick, N.; Shenouda, M.; Sadek, B.; Smith, B. L.; Taghian, A.; Specht, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S55 EP S56 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700146 ER PT J AU Schmidt, B Chang, KK Maduekwe, UN Look-Hong, N Yang, H Rattner, DW Lauwers, GY Mullen, JT Yoon, SS AF Schmidt, B. Chang, K. K. Maduekwe, U. N. Look-Hong, N. Yang, H. Rattner, D. W. Lauwers, G. Y. Mullen, J. T. Yoon, S. S. TI D2 Lymphadenectomy and Ex Vivo Dissection into Node Stations for Gastric Adenocarcinoma Ensures Optimal Staging SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Schmidt, B.; Chang, K. K.; Maduekwe, U. N.; Look-Hong, N.; Rattner, D. W.; Lauwers, G. Y.; Mullen, J. T.; Yoon, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yang, H.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S133 EP S134 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700391 ER PT J AU Tang, R Kansal, KJ Lei, L Coopey, S Colwell, AS Gadd, MA Specht, MC Taghian, A Austen, WG Smith, BL AF Tang, R. Kansal, K. J. Lei, L. Coopey, S. Colwell, A. S. Gadd, M. A. Specht, M. C. Taghian, A. Austen, W. G., Jr. Smith, B. L. TI Impact of Prior Radiation Therapy on Post-operative Complications in Nipple Sparing Mastectomy and Immediate Reconstruction: A Case-Matched, Risk-Adjusted Cohort Study SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Tang, R.; Kansal, K. J.; Lei, L.; Coopey, S.; Colwell, A. S.; Gadd, M. A.; Specht, M. C.; Taghian, A.; Austen, W. G., Jr.; Smith, B. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S39 EP S39 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700095 ER PT J AU Webb, ML Cady, B Michaelson, JS Bush, DM Calvillo, KZ Kopans, DB Smith, BL AF Webb, M. L. Cady, B. Michaelson, J. S. Bush, D. M. Calvillo, K. Zabicki Kopans, D. B. Smith, B. L. TI A Failure Analysis of Invasive Breast Cancer: Most Deaths from Disease Occur in Women Not Regularly Screened SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Webb, M. L.; Cady, B.; Michaelson, J. S.; Bush, D. M.; Smith, B. L.] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Breast Program, Boston, MA 02114 USA. [Calvillo, K. Zabicki] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kopans, D. B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S53 EP S53 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700138 ER PT J AU Yoon, CH Le, J Ibrahim, N Gold, J Bertagnolli, MM Hodi, FS AF Yoon, C. H. Le, J. Ibrahim, N. Gold, J. Bertagnolli, M. M. Hodi, F. S. TI Tumor Heterogeneity in Metastatic Melanoma Patients with BRAF/NRAS Mutations SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 06-09, 2013 CL National Harbor, MD SP Soc Surg Oncol (SSO) C1 [Yoon, C. H.; Le, J.; Gold, J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ibrahim, N.; Bertagnolli, M. M.; Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2013 VL 20 SU 1 BP S23 EP S23 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XR UT WOS:000318174700052 ER PT J AU Elfiky, AA Jiang, ZY AF Elfiky, Aymen A. Jiang, Zhenyang TI The PI3 Kinase Signaling Pathway in Prostate Cancer SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Androgen receptor; mammalian target of rapamycin; phosphatidylinositol 3-kinase; prostate cancer; PTEN ID ANDROGEN RECEPTOR FUNCTION; PTEN GENOMIC DELETION; 4-PHOSPHATASE TYPE-II; TRANSCRIPTION FACTORS; TUMOR-SUPPRESSOR; HORMONAL-THERAPY; CELL-POPULATIONS; FISH ANALYSIS; MTOR COMPLEX; GENE FUSIONS AB Despite recent advances in our understanding of the biological basis of prostate cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is increasingly implicated in a number of malignancies, including prostate carcinogenesis. In this review, we detail the role of this pathway in the pathogenesis of prostate cancer and the therapeutic implications of targeting it. C1 [Elfiky, Aymen A.; Jiang, Zhenyang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Elfiky, AA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Aymen_Elfiky@dfci.harvard.edu NR 93 TC 8 Z9 8 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD FEB PY 2013 VL 13 IS 2 BP 157 EP 164 PG 8 WC Oncology SC Oncology GA 130MW UT WOS:000317923100005 PM 23215719 ER PT J AU Sikora, D Moran, E Orlich, F Hall, TA Kovacs, EA Delahaye, J Clemons, TE Kuhlthau, K AF Sikora, Darryn Moran, Erin Orlich, Felice Hall, Trevor A. Kovacs, Erica A. Delahaye, Jennifer Clemons, Traci E. Kuhlthau, Karen TI The relationship between family functioning and behavior problems in children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Family functioning; Behavior problems; Impact on parents; Marriage; Siblings ID QUALITY-OF-LIFE; DEVELOPMENTAL DELAY; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; MENTAL-HEALTH; PARENTING STRESS; MOTHERS; IMPACT; DISABILITIES; ADJUSTMENT AB Although it is well known that families of children with an autism spectrum disorder (ASD) are at risk for increased stress and other problems, little is known about what child characteristics may mediate that risk. To address the impact of child behavior problems on family health, we examined data collected from 136 families raising children with ASD. Children were divided into groups based on parent responses to the Child Behavior Checklist (CBCL): low versus high internalizing and low versus high externalizing behavior problems. Family functioning was measured using the Family Impact Questionnaire, Revised (FIQ-R). Results of ANCOVA analyses indicated significant group differences in FIQ-R domains of Negative Attitudes About Parenting, Social Relationships, Sibling Impact, and Impact to Marriage when comparing externalizing behaviors. None of the FIQ-R domains demonstrated group differences when comparing internalizing behaviors. Correlation coefficients indicated moderately strong associations between higher externalizing behaviors and poorer family functioning, with the most significant associations among child behavior and increased negativity in parenting perceptions and poorer social functioning. This study provides information regarding co-occurring behaviors that have the strongest negative association with family functioning and the domains of family functioning most vulnerable to the severity of such behaviors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sikora, Darryn; Moran, Erin] Oregon Hlth & Sci Univ, Child Dev & Rehabil Ctr, Portland, OR 97201 USA. [Orlich, Felice] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Orlich, Felice] Seattle Childrens Hosp, Autism Program, CAC Autism Ctr, Seattle, WA 98105 USA. [Hall, Trevor A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kovacs, Erica A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Delahaye, Jennifer] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Clemons, Traci E.] EMMES Corp, Rockville, MD 20850 USA. [Kuhlthau, Karen] Harvard Univ, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat,Med Sch, Boston, MA 02114 USA. RP Sikora, D (reprint author), Providence Hlth & Serv, 814 NE 47th Ave, Portland, OR 97213 USA. EM darryn.sikora@providence.org NR 65 TC 11 Z9 11 U1 13 U2 54 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD FEB PY 2013 VL 7 IS 2 BP 307 EP 315 DI 10.1016/j.rasd.2012.09.006 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 134FD UT WOS:000318194700011 ER PT J AU McLaughlin, VV Langer, A Tan, M Clements, PJ Oudiz, RJ Tapson, VF Channick, RN Rubin, LJ AF McLaughlin, Vallerie V. Langer, Anatoly Tan, Mary Clements, Philip J. Oudiz, Ronald J. Tapson, Victor F. Channick, Richard N. Rubin, Lewis J. CA Pulm Arterial Hypertension-Quality TI Contemporary Trends in the Diagnosis and Management of Pulmonary Arterial Hypertension An Initiative to Close the Care Gap SO CHEST LA English DT Article ID CONTINUOUS INTRAVENOUS EPOPROSTENOL; CLINICAL-PRACTICE GUIDELINES; CONTROLLED-TRIAL; REGISTRY; THERAPY; SURVIVAL; DISEASE; PROSTACYCLIN; REVEAL AB Background: The Pulmonary Arterial Hypertension-Quality Enhancement Research Initiative (PAH-QuERI) was created to help clinicians to implement a guidelines-based approach to the diagnosis and management of pulmonary arterial hypertension (PAR). Patients with PAR represent a heterogeneous population, and physician evaluation and treatment paradigms may vary considerably. Methods: Using an electronic data management system, participating physicians recorded data on diagnostic workup, disease management, and outcomes of patients with PAH. Queries were generated automatically following each follow-up visit if the tests recommended by the American College of Chest Physicians (ACCP) were not performed at least once. Results: Of 791 patients enrolled in PAH-QuERI, 77% were women; 64% received a diagnosis >3 months prior to enrollment; 9% were in New York Heart Association functional class I, 39% in II, 48% in III, and 5% in IV; and the median age was 55 years (interquartile range, 45-66 years). At enrollment, all ACCP-recommended tests had been performed in only 6% of patients. The automated program generated 1,530 reminders for 642 patients (81%) with validated enrollment data. The proportion of recommended tests performed was 91% for CBC count, 91% for liver function test, 50% for connective tissue disease screen, 29% for HIV screen, 88% for chest radiograph, 82% for ECG, 97% for two-dimensional echocardiogram, 83% for pulmonary function tests, 41% for oximetry, 57% for ventilation/perfusion scan, 79% for 6-min walk distance, and 90% for right-sided heart catheterization. Regarding management, 78% of patients were on disease-specific therapy, and the use of these therapies tended to increase with the functional disability of the patient. One hundred seventy patients were taking calcium channel blockers, 91 specifically for PAR. Only six of 91 patients (7%) who received calcium channel blockers specifically for PAH had met the current guideline for acute vasoreactivity. Conclusions: When comparing reported clinical practice with ACCP guidelines-recommended strategies, a diagnostic care gap is apparent such that certain essential and recommended diagnostic tests may be underused despite the availability of detailed guidelines and reminders. CHEST 2013; 143(2):324-332 C1 [McLaughlin, Vallerie V.] Univ Michigan Hlth Syst, Pulm Hypertens Program, Ann Arbor, MI USA. [Langer, Anatoly; Tan, Mary] Canadian Heart Res Ctr, Toronto, ON, Canada. [Clements, Philip J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Oudiz, Ronald J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Tapson, Victor F.] Duke Univ, Med Ctr, Durham, NC USA. [Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rubin, Lewis J.] Univ Calif San Diego, La Jolla, CA USA. RP McLaughlin, VV (reprint author), Univ Michigan, Ctr Cardiovasc, Pulm Hypertens Program, 1500 E Med Ctr Dr,SPC 5853, Ann Arbor, MI 48109 USA. EM vmclaugh@umich.edu FU Actelion Pharmaceuticals US, Inc; Gilead; Novartis AG; United Therapeutics Corporation; Lung LLC; Pfizer, Inc; GlaxoSimithKline plc; Ikaria, Inc; Bayer AG FX The authors have reported to CHEST the following conflicts of interest: Dr McLaughlin has served as a consultant and speaker for Actelion Pharmaceuticals US, Inc; Bayer AG; Gilead; and United Therapeutics Corporation. She has also received research funding for multicenter trials from Actelion Pharmaceuticals US, Inc; Gilead; Novartis AG; and United Therapeutics Corporation. Dr Langer has received research and educational grants from Actelion Pharmaceuticals US, Inc, and United Therapeutics Corporation. Dr Clements has served as a consultant for Gilead. Dr Oudiz has served as a consultant and speaker and received research funding for multicenter trials from Actelion Pharmaceuticals US, Inc; Bayer AG; Gilead; Lung LLC; Pfizer, Inc; and United Therapeutics Corporation. Dr Tapson has served as a consultant for and received research funding from Actelion Pharmaceuticals US, Inc; Gilead; GlaxoSimithKline plc; Lung LLC; Novartis AG; and United Therapeutics Corporation. Dr Channick has served as a consultant for Actelion Pharmaceuticals US, Inc; Gilead; and Ikaria, Inc. He has also received research grants from Actelion Pharmaceuticals US, Inc; Bayer AG; Gilead; Pfizer, Inc; and United Therapeutics Corporation. Dr Rubin has served as a consultant for Actelion Pharmaceuticals US, Inc; Pfizer, Inc; United Therapeutics Corporation; Lung LLC; National Heart, Lung, and Blood Institute; Gilead; Aires Pharmaceuticals, Inc; GlaxoSmithKline plc; Bayer AG; Geno Pharmaceuticals Ltd; Cytokinetics, Inc; and mondoBIOTECH Holding AG. He has served on the scientific advisory committee for United Therapeutics Corporation. He is a stock shareholder for United Therapeutics Corporation; Geno Pharmaceuticals Ltd; and Aires Pharmaceuticals, Inc. Ms Tan has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 24 TC 31 Z9 32 U1 0 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2013 VL 143 IS 2 BP 324 EP 332 DI 10.1378/chest.11-3060 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 129VC UT WOS:000317871100011 PM 22910999 ER PT J AU Jalian, HR Jalian, CA Avram, MM AF Jalian, H. Ray Jalian, Chris A. Avram, Mathew M. TI Common Causes of Injury and Legal Action in Laser Surgery SO JAMA DERMATOLOGY LA English DT Article ID Q-SWITCHED RUBY; CARBON-DIOXIDE; HAIR REMOVAL; MALPRACTICE AB Objective: To identify common causes of legal action, injuries, claims, and decisions related to medical professional liability claims stemming from cutaneous laser surgery. Design: Search of online public legal documents using a national database. Main Outcome Measures: Frequency and nature of cases, including year of litigation, location and certification of provider, injury sustained, cause of legal action, verdict, and indemnity payment. Results: From 1985 to 2012, the authors identified 174 cases related to injury stemming from cutaneous laser surgery. The incidence of litigation related to laser surgery shows an increasing trend, with peak occurrence in 2010. Laser hair removal was the most common litigated procedure. Nonphysician operators accounted for a substantial subset of these cases, with their physician supervisors named as defendants, despite not performing the procedure. Plastic surgery was the specialty most frequently litigated against. Of the preventable causes of action, the most common was failure to obtain an informed consent. Of the 120 cases with public decisions, 61 (50.8%) resulted in decisions in favor of the plaintiff. The mean indemnity payment was $380 719. Conclusions: Claims related to cutaneous laser surgery are increasing and result in indemnity payments that exceed the previously reported average across all medical specialties. Nonphysicians performing these procedures will be held to a standard of care corresponding to an individual with appropriate training; thus, physicians are ultimately responsible for the actions of their nonphysician agents. JAMA Dermatol. 2013;149(2):188-193 C1 [Jalian, H. Ray; Avram, Mathew M.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jalian, Chris A.] Columbia Law Sch, New York, NY USA. RP Jalian, HR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 40 Blossom St,Thier 2,Room 204, Boston, MA 02114 USA. EM HJalian@partners.org NR 13 TC 19 Z9 19 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD FEB PY 2013 VL 149 IS 2 BP 188 EP 193 DI 10.1001/jamadermatol.2013.1384 PG 6 WC Dermatology SC Dermatology GA 127CH UT WOS:000317672300011 PM 23426473 ER PT J AU Hausauer, AK Maurer, T Leslie, KS Parvataneni, R Stuart, SE Chren, MM AF Hausauer, Amelia K. Maurer, Toby Leslie, Kieron S. Parvataneni, Rupa Stuart, Sarah E. Chren, Mary-Margaret TI Recurrence After Treatment of Cutaneous Basal Cell and Squamous Cell Carcinomas in Patients Infected With Human Immunodeficiency Virus SO JAMA DERMATOLOGY LA English DT Letter ID MALIGNANCIES C1 [Hausauer, Amelia K.; Maurer, Toby; Leslie, Kieron S.; Parvataneni, Rupa; Stuart, Sarah E.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Maurer, Toby; Leslie, Kieron S.] San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94110 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chren, MM (reprint author), Mt Zion Canc Res Bldg,2340 Sutter St,Room N412,Ma, San Francisco, CA 94143 USA. EM chrenm@derm.ucsf.edu FU NIAMS NIH HHS [K24 AR052667, R01 AR054983] NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD FEB PY 2013 VL 149 IS 2 BP 239 EP 241 DI 10.1001/2013.jamadermatol.245 PG 4 WC Dermatology SC Dermatology GA 127CH UT WOS:000317672300029 PM 23426494 ER PT J AU Ibrahimi, OA Sakamoto, FH Anderson, RR AF Ibrahimi, Omar A. Sakamoto, Fernanda H. Anderson, R. Rox TI Picosecond Laser Pulses for Tattoo Removal: A Good, Old Idea SO JAMA DERMATOLOGY LA English DT Letter ID PIGMENT C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT USA. [Ibrahimi, Omar A.; Sakamoto, Fernanda H.; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Ibrahimi, OA (reprint author), Univ Connecticut, Ctr Hlth, 21 South Rd,2nd Flr, Farmington, CT 06032 USA. EM omar.ibrahimi@gmail.com NR 5 TC 6 Z9 6 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD FEB PY 2013 VL 149 IS 2 BP 241 EP 241 DI 10.1001/jamadermatol.2013.2136 PG 1 WC Dermatology SC Dermatology GA 127CH UT WOS:000317672300030 PM 23426495 ER PT J AU Bosley, JC Zhao, NW Hill, S Shofer, FS Asch, DA Becker, LB Merchant, RM AF Bosley, Justin C. Zhao, Nina W. Hill, Shawndra Shofer, Frances S. Asch, David A. Becker, Lance B. Merchant, Raina M. TI Decoding twitter: Surveillance and trends for cardiac arrest and resuscitation communication SO RESUSCITATION LA English DT Article DE Cardiopulmonary resuscitation; Heart arrest; Defibrillation; Resuscitation; Social media ID AMERICAN-HEART-ASSOCIATION; EMERGENCY CARDIOVASCULAR CARE; CARDIOPULMONARY-RESUSCITATION; SOCIAL MEDIA; SURVIVAL AB Aim of the study: Twitter has over 500 million subscribers but little is known about how it is used to communicate health information. We sought to characterize how Twitter users seek and share information related to cardiac arrest, a time-sensitive cardiovascular condition where initial treatment often relies on public knowledge and response. Methods: Tweets published April-May 2011 with keywords cardiac arrest, CPR, AED, resuscitation, heart arrest, sudden death and defib were identified. Tweets were characterized by content, dissemination, and temporal trends. Tweet authors were further characterized by: self-identified background, tweet volume, and followers. Results: Of 62,163 tweets (15,324, 25%) included resuscitation/cardiac arrest-specific information. These tweets referenced specific cardiac arrest events (1130, 7%), CPR performance or AED use (6896, 44%), resuscitation-related education, research, or news media (7449, 48%), or specific questions about cardiac arrest/resuscitation (270, 2%). Regarding dissemination (1980, 13%) of messages were retweeted. Resuscitation specific tweets primarily occurred on weekdays. Most users (10,282, 93%) contributed three or fewer tweets during the study time frame. Users with more than 15 resuscitation-specific tweets in the study time frame had a mean 1787 followers and most self-identified as having a healthcare affiliation. Conclusion: Despite a large volume of tweets, Twitter can be filtered to identify public knowledge and information seeking and sharing about cardiac arrest. To better engage via social media, healthcare providers can distil tweets by user, content, temporal trends, and message dissemination. Further understanding of information shared by the public in this forum could suggest new approaches for improving resuscitation related education. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Bosley, Justin C.; Zhao, Nina W.; Shofer, Frances S.; Becker, Lance B.; Merchant, Raina M.] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hill, Shawndra] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.; Merchant, Raina M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, 423 Guardian St,Blockley Hall, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIH [10714038]; Physio-Control Seattle, Washington; Zoll Medical, Boston MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD FX Merchant: Grant/research support: NIH, K23 grant 10714038, Pilot funding: Physio-Control Seattle, Washington; Zoll Medical, Boston MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington.; Becker: Speaker honoraria/consultant fees: Philips Healthcare, Seattle, WA. Institutional grant/research support: Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, Washington. NR 28 TC 22 Z9 23 U1 2 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD FEB PY 2013 VL 84 IS 2 BP 206 EP 212 DI 10.1016/j.resuscitation.2012.10.017 PG 7 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 123UH UT WOS:000317416100029 PM 23108239 ER PT J AU Lazaridou, A Kalogianni, C AF Lazaridou, Asimina Kalogianni, Christina TI Mindfulness and sexuality SO SEXUAL AND RELATIONSHIP THERAPY LA English DT Article DE mindfulness; sexuality; behavior ID STRESS REDUCTION; METAANALYSIS; HEALTH; MEDITATION; MEDICINE; ANXIETY; WOMEN AB Mindfulness seems to associate with positive effects on health and overall wellbeing. However, little research has indicated association between mindfulness and sexuality. The goal of this study was to test the hypothesis that mindfulness correlates with sexuality in healthy people. We conducted a cross-sectional study with people who practice yoga or meditation (n = 51), people who have done a sport for over 10years (n = 21) and people who have done none of the above (n = 145) by studying correlations between mindfulness and sexuality. A total of 215 men and women participated in this study (M = 31.61, SD = 9.24). We measured mindfulness and sexuality by distri-buting the Langer's Mindfulness Scale and the Multidimensional Sexuality Questionnaire. We explored whether mindfulness subscales correlate with any of the sexuality subscales in these three study groups, irrespectively. People in the meditation/yoga group had been practicing mindfulness and different meditative practices (including vipassana and yoga) for over 10years. We found significant higher scores in the novelty-seeking component in people who meditate compared to athletes. Even though our results showed that the group of people who do a sport have less sexual anxiety and sexual depression compared to the meditators, these results were not at a statistically significant level. Additionally, no significant differences were found between the other groups. We found positive correlations between all mindfulness subscales (engagement, novelty seeking, novelty producing and flexibility) and sexual motivation, and between novelty seeking and sexual consciousness. Our findings seem to indicate that mindfulness correlates positively with sexual motivation and sexual consiousness. In particular, people who practice meditation or yoga showed higher levels in novelty seeking (mindfulness subscale) compared to people who play sport. Novelty seeking might be an important component in affecting sexuality. C1 [Lazaridou, Asimina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Kalogianni, Christina] Catholic Univ Louvain, Louvain, Belgium. RP Lazaridou, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM asilaz@nmr.mgh.harvard.edu NR 41 TC 7 Z9 7 U1 3 U2 25 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1468-1994 J9 SEX RELATSH THER JI Sex. Relatsh. Ther. PD FEB 1 PY 2013 VL 28 IS 1-2 BP 29 EP 38 DI 10.1080/14681994.2013.773398 PG 10 WC Psychology, Clinical SC Psychology GA 122HE UT WOS:000317308400004 ER PT J AU Elder, JB Chiocce, EA AF Elder, J. Bradley Chiocce, E. Antonio TI Molecular and Genetic Characterization of Meningiomas: Future Predictive Assays and "Personalized" Treatment SO WORLD NEUROSURGERY LA English DT Editorial Material DE Atypical meningioma; Copy number; Copy number gains; Gene amplification; Meningioma; Multiplex ligation-dependent probe amplification; Oncogene C1 [Elder, J. Bradley] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA. [Chiocce, E. Antonio] Harvard Univ, Sch Med, Dept Neurosurg, Inst Neurosci,Brigham & Womens Faulkner Hosp, Boston, MA USA. [Chiocce, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocce, EA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM EAChiocca@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 J9 WORLD NEUROSURG JI World Neurosurg. PD FEB PY 2013 VL 79 IS 2 BP 247 EP 248 DI 10.1016/j.wneu.2011.10.005 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 125JV UT WOS:000317537000009 PM 22120235 ER PT J AU Wang, Y Wang, H Xia, JX Liang, TT Wang, GJ Li, XK Yang, YG AF Wang, Yi Wang, Hui Xia, Jinxing Liang, Tingting Wang, Guanjun Li, Xiaokun Yang, Yong-Guang TI Activated CD8 T cells acquire NK1.1 expression and preferentially locate in the liver in mice after allogeneic hematopoietic cell transplantation SO IMMUNOLOGY LETTERS LA English DT Article DE CD8 T cells; NK1.1(+)CD8(+) T cells; Allogeneic hematopoietic cell transplantation; Liver ID IFN-GAMMA; NKT CELLS; DISEASE; EXPANSION; RECEPTORS; MOLECULES AB Immune cells expressing both NK and T cell markers include CD1d-dependent NKT cells and CD1d-independent NKT-like cells. We now describe the presence of NK1.1(+)CD8(+) T cells in the liver, but not other tissues (spleen, bone marrow, thymus or peripheral blood) in mice receiving allogeneic hematopoietic cell transplantation (allo-HCT). These cells are CD1d-independent TCR alpha beta(+) T cells with an effector/memory CD44(hi)CD62L(-) phenotype, and do not express Ly49 receptors. Furthermore, these cells were derived from donor splenocytes, but not bone marrow cells. Depletion of CD8(+), but not NK1.1(+), cells from donor splenocytes prior to transplantation prevented the generation of NK1.1(+)CD8(+) T cells, indicating that these cells arose from donor NK1.1(-)CD8(+) splenic T cells. These results provide direct evidence that donor CD8(+) T cells can acquire NK1.1 expression upon activation in allo-HCT recipients and that these NK1.1(+)CD8(+) NKT-like cells maintain an effector/memory phenotype and persist in the recipients with preferential localization in the liver. (c) 2012 Elsevier B.V. All rights reserved. C1 [Wang, Yi; Li, Xiaokun] Wenzhou Med Coll, Sch Pharmaceut Sci, Key Lab Biotechnol Pharmaceut Engn Zhejiang Prov, Wenzhou 325035, Peoples R China. [Wang, Yi; Wang, Hui; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wang, Hui; Xia, Jinxing; Yang, Yong-Guang] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. [Liang, Tingting; Wang, Guanjun; Yang, Yong-Guang] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. RP Yang, YG (reprint author), Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, 630 W 168th St, New York, NY 10032 USA. EM yy2324@columbia.edu RI Xia, Jinxing/E-5658-2015 FU NIH [CA111519, AI064569]; Zhejiang Province Extremely Key Subject Building Funding [2012R10042-11]; Natural Science Funding of China [81102452] FX We thank Drs. Haowei Li and Ben Sprangers for critical review of the manuscript, Ms. Shumei Wang for technical support, and Mr. Orlando Moreno for outstanding animal husbandry. This study was supported by grants from NIH (CA111519 and AI064569), Zhejiang Province Extremely Key Subject Building Funding (2012R10042-11), and Natural Science Funding of China (81102452). NR 12 TC 1 Z9 1 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD FEB PY 2013 VL 150 IS 1-2 BP 75 EP 78 DI 10.1016/j.imlet.2012.12.009 PG 4 WC Immunology SC Immunology GA 122JW UT WOS:000317315400010 PM 23291124 ER PT J AU Yan, QS Xu, R Zhu, LY Cheng, X Wang, Z Manis, J Shipp, MA AF Yan, Qingsheng Xu, Rong Zhu, Liya Cheng, Xin Wang, Zhe Manis, John Shipp, Margaret A. TI BAL1 and Its Partner E3 Ligase, BBAP, Link Poly(ADP-Ribose) Activation, Ubiquitylation, and Double-Strand DNA Repair Independent of ATM, MDC1, and RNF8 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID B-CELL LYMPHOMAS; DAMAGE RESPONSE; PARP INHIBITORS; PROTEINS; CHROMATIN; BREAKS; BRCA1; SURVIVAL; TARGETS; CANCER AB The BAL1 macrodomain-containing protein and its partner E3 ligase, BBAP, are overexpressed in chemotherapy-resistant lymphomas. BBAP selectively ubiquitylates histone H4 and indirectly promotes early 53BP1 recruitment to DNA damage sites. However, neither BBAP nor BAL1 has been directly associated with a DNA damage response (DDR), and the function of BAL1 remains undefined. Herein, we describe a direct link between rapid and short-lived poly(ADP-ribose) (PAR) polymerase 1 (PARP1) activation and PARylation at DNA damage sites, PAR-dependent recruitment of the BAL1 macrodomain-containing protein and its partner E3 ligase, local BBAP-mediated ubiquitylation, and subsequent recruitment of the checkpoint mediators 53BP1 and BRCA1. The PARP1-dependent localization of BAL1-BBAP functionally limits both early and delayed DNA damage and enhances cellular viability independent of ATM, MDC1, and RNF8. These data establish that BAL1 and BBAP are bona fide members of a DNA damage response pathway and are directly associated with PARP1 activation, BRCA1 recruitment, and double-strand break repair. C1 [Yan, Qingsheng; Xu, Rong; Zhu, Liya; Cheng, Xin; Wang, Zhe; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Manis, John] Childrens Hosp Boston, Boston, MA USA. [Manis, John] Harvard Univ, Sch Med, Joint Program Transfus Med, Boston, MA USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu FU NIH [PO1CA092625, CA133781] FX We acknowledge support from NIH grants PO1CA092625 (M.A.S.) and CA133781 (J.M.). NR 31 TC 26 Z9 29 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2013 VL 33 IS 4 BP 845 EP 857 DI 10.1128/MCB.00990-12 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121TK UT WOS:000317267000016 PM 23230272 ER PT J AU Demers, M Wagner, DD AF Demers, Melanie Wagner, Denisa D. TI Neutrophil extracellular traps A new link to cancer-associated thrombosis and potential implications for tumor progression SO ONCOIMMUNOLOGY LA English DT Editorial Material DE cancer; NETs; metastasis; neutrophils; thrombosis; tumor progression ID INNATE IMMUNITY; LUNG METASTASIS; DNA TRAPS AB Cancers prime neutrophils to release extracellular DNA traps through the systemic release of granulocyte colony-stimulating factor (G-CSF). We recently showed that these circulating neutrophil extracellular traps (NETs) promote the establishment of a pro-thrombotic state. The role of NETs in cancer biology and tumor progression may prove much more than an unfortunate side effect of cancer. C1 [Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. EM Denisa.Wagner@childrens.harvard.edu FU NHLBI NIH HHS [R01 HL102101] NR 10 TC 31 Z9 32 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD FEB PY 2013 VL 2 IS 2 AR e22946 DI 10.4161/onci.22946 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 121SF UT WOS:000317263800025 PM 23526174 ER PT J AU Villablanca, EJ AF Villablanca, Eduardo J. TI Retinoic acid-producing DCs and gut-tropic FOXP3(+) regulatory T cells in the induction of oral tolerance SO ONCOIMMUNOLOGY LA English DT Editorial Material DE dendritic cells; FOXP3; gut homing; oral tolerance; retinoic acid ID MICROBIOTA AB The systemic unresponsiveness of the immune system to orally administered antigens is known as oral tolerance. Recent findings describe a new step for the induction of oral tolerance, consisting in the homing of FOXP3(+) regulatory T cells to the small bowel and the local acquisition of full immunosuppressive capacities, a process in which retinoic acid-producing dendritic cells might play a crucial role. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02215 USA. RP Villablanca, EJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02215 USA. EM Villablanca.Eduardo@mgh.harvard.edu RI Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 NR 8 TC 4 Z9 4 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD FEB PY 2013 VL 2 IS 2 AR e22987 DI 10.4161/onci.22987 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 121SF UT WOS:000317263800030 ER PT J AU Reis, JP Loria, CM Launer, LJ Sidney, S Liu, K Jacobs, DR Zhu, N Lloyd-Jones, DM He, K Yaffe, K AF Reis, Jared P. Loria, Catherine M. Launer, Lenore J. Sidney, Stephen Liu, Kiang Jacobs, David R., Jr. Zhu, Na Lloyd-Jones, Donald M. He, Ka Yaffe, Kristine TI Cardiovascular health through young adulthood and cognitive functioning in midlife SO ANNALS OF NEUROLOGY LA English DT Article ID RISK-FACTORS; METABOLIC SYNDROME; INCIDENT DEMENTIA; BLOOD-PRESSURE; US ADULTS; IMPAIRMENT; LIFE; DECLINE; CARDIA; ASSOCIATION AB Objective A study was undertaken to examine the association between overall cardiovascular health as recently defined by the American Heart Association in young adulthood to middle age and cognitive function in midlife. Overall ideal cardiovascular health incorporates 7 metrics, including the avoidance of overweight or obesity, a healthful diet, nonsmoking, and physical activity, total cholesterol, blood pressure, and fasting glucose at goal levels. Methods This analysis of the Coronary Artery Risk Development in Young Adults study, a multicenter community-based study with 25 years of follow-up, included 2,932 participants aged 18 to 30 years at baseline (year 0) who attended follow-up examinations at years 7 and 25. Cardiovascular health metrics were measured at each examination. The Digit Symbol Substitution Test (DSST), modified Stroop test, and Rey Auditory Verbal Learning Test (RAVLT) were completed at year 25. Results A greater number of ideal cardiovascular metrics in young adulthood and middle age were independently associated with better cognitive function in midlife (p for trend < 0.01, for all). Specifically, each additional ideal metric was associated with 1.32 more symbols on the DSST (95% confidence interval [CI] = 0.93 1.71), a 0.77-point lower interference score on the Stroop test (95% CI=1.03 to 0.45), and 0.12 more words on the RAVLT (95% CI = 0.04 to 0.20). Participants who had 5 ideal metrics at a greater number of the 3 examinations over the 25-year period exhibited better performance on each cognitive test in middle age (p for trend < 0.01, for all). Interpretation Ideal cardiovascular health in young adulthood and its maintenance to middle age is associated with better psychomotor speed, executive function, and verbal memory in midlife. ANN NEUROL 2013;73:170179 C1 [Reis, Jared P.; Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Sidney, Stephen] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Jacobs, David R., Jr.; Zhu, Na] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [He, Ka] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [He, Ka] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10197, Bethesda, MD 20892 USA. EM reisjp@mail.nih.gov FU National Heart, Lung, and Blood Institute; University of Alabama at Birmingham [N01-HC95095, N01-HC48047]; Kaiser Foundation Research Institute [N01-HC48050]; Northwestern University [N01-HC48049]; University of Minnesota [N01-HC48048] FX CARDIA is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (N01-HC95095, N01-HC48047), Kaiser Foundation Research Institute (N01-HC48050), Northwestern University (N01-HC48049), and University of Minnesota (N01-HC48048). NR 38 TC 40 Z9 41 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2013 VL 73 IS 2 BP 170 EP 179 DI 10.1002/ana.23836 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 113UA UT WOS:000316693200006 PM 23443990 ER PT J AU Fitzgerald, KC O'Reilly, EJ Fondell, E Falcone, GJ McCullough, ML Park, Y Kolonel, LN Ascherio, A AF Fitzgerald, Kathryn C. O'Reilly, Eilis J. Fondell, Elinor Falcone, Guido J. McCullough, Marjorie L. Park, Yikyung Kolonel, Laurence N. Ascherio, Alberto TI Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies SO ANNALS OF NEUROLOGY LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; SOCIETY CANCER PREVENTION; BASE-LINE CHARACTERISTICS; RETIRED-PERSONS DIET; MOTOR-NEURON DISEASE; NATIONAL-INSTITUTES; OXIDATIVE STRESS; SURVIVAL; WOMEN AB Objective Prior research has suggested the possible role of oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS). Prospective data examining dietary antioxidants such carotenoids and vitamin C are limited. Methods Risk of ALS associated with carotenoid and vitamin C intake was investigated in 5 prospective cohorts: the National Institutes of HealthAssociation of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study (HPFS), and the Nurses Health Study (NHS). ALS deaths were documented using the National Death Index, and confirmed nonfatal ALS cases were included from HPFS and NHS. A total of 1,153 ALS deaths occurred among 1,100,910 participants (562,942 men; 537,968 women). Participants were categorized into cohort-specific quintiles of intake for dietary variables. We applied Cox proportional hazards regression to calculate cohort-specific risk ratios (RRs), and pooled results using random-effects methods. Results A greater total major carotenoids intake was associated with a reduced risk of ALS (pooled, multivariate-adjusted RR for the highest to the lowest quintile = 0.75, 95% confidence interval [CI] = 0.610.91, p for trend = 0.004). Individually, higher dietary intakes of -carotene and lutein were inversely associated with ALS risk. The pooled multivariate RRs comparing the highest to the lowest quintile for -carotene and lutein were 0.85 (95% CI = 0.641.13, p for trend = 0.03) and 0.79 (95% CI = 0.640.96, p for trend = 0.01), respectively. Lycopene, -cryptoxanthin, and vitamin C were not associated with reduced risk of ALS. Interpretation Consumption of foods high in carotenoids may help prevent or delay onset of ALS. ANN NEUROL 2013;73:236245 C1 [Fitzgerald, Kathryn C.; O'Reilly, Eilis J.; Fondell, Elinor; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [O'Reilly, Eilis J.; Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. [Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. RP Fitzgerald, KC (reprint author), 665 Huntington Ave, Boston, MA 02115 USA. EM hpkcf@channing.harvard.edu RI Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Park, Yikyung/0000-0002-6281-489X FU NIH/National Institute of Neurological Diseases and Stroke [R01 NS045893]; NIH/NCI [R37 CA54281]; neurological diseases and stroke (NIH) [P01 CA87969]; NIH [P01 CA055075]; Blanceflor Foundation (Stockholm, Sweden); Michael J Fox Foundation; Accelerated Cure Project; F. Hoffmann-La Roche; Merck Serono FX This work was supported by grant R01 NS045893 from the NIH/National Institute of Neurological Diseases and Stroke. The multiethnic cohort study was supported by NIH/NCI R37 CA54281. Nurses Health Study is funded by neurological diseases and stroke (NIH) program project P01 CA87969 and Health Professional Follow-up Study by NIH program project P01 CA055075. E.F. received a postdoctoral scholarship from the Blanceflor Foundation (Stockholm, Sweden).; K.C.F.: grants/grants pending, NIH. E.J.O.: grants/grants pending, NIH. A.A.: grants/grants pending, National Institutes of Health, Michael J Fox Foundation, Accelerated Cure Project; speaking fees, F. Hoffmann-La Roche, Merck Serono. NR 39 TC 19 Z9 21 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2013 VL 73 IS 2 BP 236 EP 245 DI 10.1002/ana.23820 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 113UA UT WOS:000316693200012 PM 23362045 ER PT J AU Cea, M Cagnetta, A Gobbi, M Patrone, F Richardson, PG Hideshima, T Anderson, KC AF Cea, Michele Cagnetta, Antonia Gobbi, Marco Patrone, Franco Richardson, Paul G. Hideshima, Teru Anderson, Kenneth C. TI New Insights into the Treatment of Multiple Myeloma with Histone Deacetylase Inhibitors SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Multiple myeloma; HDACIs; apoptosis; proteasome inhibitor; novel therapy ID SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; DNA-DAMAGE; LEUKEMIA-CELLS; HEMATOLOGIC MALIGNANCIES; ANTILEUKEMIA ACTIVITY; DEPENDENT APOPTOSIS; CLINICAL-RESPONSES; TUMOR ANGIOGENESIS; TRANSFORMED-CELLS AB Multiple Myeloma (MM) is a common hematologic malignancy of plasma cells representing an excellent model of epigenomics dysregulation in human disease. Importantly, these findings, in addition to providing a better understanding of the underlying molecular changes leading to this malignance, furnish the basis for an innovative therapeutic approach. Histone deacetylase inhibitors (HDACIs), including Vorinostat and Panobinostat, represent a novel class of drugs targeting enzymes involved in epigenetic regulation of gene expression, which have been evaluated also for the treatment of multiple myeloma. Although the clinical role in this setting is evolving and their precise utility remains to be determined, to date that single-agent anti-MM activity is modest. More importantly, HDACIs appear to be synergistic both in vitro and in vivo when combined with other anti-MM agents, mainly proteasome inhibitors including bortezomib. The molecular basis underlying this synergism seems to be multifactorial and involves interference with protein degradation as well as the interaction of myeloma cells with microenvironment. Here we review molecular events underling antitumor effects of HDACIs and the most recent results of clinical trials in relapsed and refractory MM. C1 [Cea, Michele; Cagnetta, Antonia; Richardson, Paul G.; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Cea, Michele; Cagnetta, Antonia; Richardson, Paul G.; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Cea, Michele; Patrone, Franco] IRCCS AOU San Martino IST, Dept Internal Med, Genoa, Italy. [Cagnetta, Antonia; Gobbi, Marco] IRCCS AOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. RP Cea, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02115 USA. EM michele_cea@dfci.harvard.edu; anderson@dfci.harvard.edu FU National Institutes of Health [RO-1 CA-50947, RO-1 CA-73878]; DF/HCC SPORE in Multiple Myeloma [PO-50100707]; American Italian Cancer Foundation; Fondazione Italiana per la Ricerca sul Cancro; International Multiple Myeloma Foundation; Associazione Italiana per la Ricerca sul Cancro FX This study is supported by National Institutes of Health (grants RO-1 CA-50947, RO-1 CA-73878), DF/HCC SPORE in Multiple Myeloma (PO-50100707); American Italian Cancer Foundation (M.C.), Fondazione Italiana per la Ricerca sul Cancro (M.C.) and International Multiple Myeloma Foundation (A.C.). K.C.A. is an American Cancer Society Council Research Professor. NR 97 TC 18 Z9 19 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD FEB PY 2013 VL 19 IS 4 BP 734 EP 744 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110MS UT WOS:000316448200012 PM 23016853 ER PT J AU Alexeeff, SE Baccarelli, AA Halonen, J Coull, BA Wright, RO Tarantini, L Bollati, V Sparrow, D Vokonas, P Schwartz, J AF Alexeeff, Stacey E. Baccarelli, Andrea A. Halonen, Jaana Coull, Brent A. Wright, Robert O. Tarantini, Letizia Bollati, Valentina Sparrow, David Vokonas, Pantel Schwartz, Joel TI Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Epigenetics; DNA methylation; blood pressure; inflammation; Bayesian model ID CARDIOVASCULAR-DISEASE RISK; CORONARY-HEART-DISEASE; PROMOTER METHYLATION; RHEUMATOID-ARTHRITIS; L1 RETROTRANSPOSONS; METABOLIC SYNDROME; HUMAN GENOME; EXPRESSION; HYPOMETHYLATION; ATHEROSCLEROSIS AB Background Methylation of deoxyribonucleic acid (DNA) is an epigenetic regulator of gene expression that changes with age, but its contribution to aging-related disorders, including high blood pressure (BP), is still largely unknown. We examined the relation of BP to the methylation of retrotransposon sequences of DNA and of selected candidate genes. Methods This investigation included 789 elderly participants in the Normative Aging Study, ranging in age from 55 to 100 years, who had longitudinal measurements of DNA methylation. In these subjects' DNA we measured the proportion of methylated sites in retrotransposable sequences and in pro-inflammatory genes, expressed as the percent of 5-methylated cytosines (%5mC) among all cytosines. From one to four methylation measurements were made for each subject between 1999 and 2009. We fit mixed-effects models, using repeated measures of BP as the outcome and DNA methylation as the explanatory variable, adjusting for confounding variables. We also fit a Bayesian mixed-effects structural equation model to account for heterogeneity in the effects of methylation sites within each gene. Results An increase in inter-quartile range (IQR) in the methylation of Alu elements was associated with an increase of 0.97 mm Hg in diastolic blood pressure (DBP) (95% CI 0.32-1.57), but no such association was observed for long interspersed nuclear element-1 (LINE-1). We also found positive associations between DBP and methylation of the genes for toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS), and a negative association between DBP and methylation of the gene for interferon-gamma (IFN-gamma). Associations between methylation and systolic blood pressure (SBP) were weaker than those between methylation and DBP. Bayesian mixed-effects structural equation model results were similar for both DBP and SBP models. Conclusions The results of our study suggest that changes in DNA methylation of some pro-inflammatory genes and retrotransposable elements are related to small changes in BP. C1 [Alexeeff, Stacey E.; Baccarelli, Andrea A.; Halonen, Jaana; Wright, Robert O.; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Alexeeff, Stacey E.; Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Baccarelli, Andrea A.; Tarantini, Letizia; Bollati, Valentina] Ca Granda Osped Maggiore Policlin IRCCS Fdn, Lab Environm Epigenet, Dept Occupat & Environm Hlth, Milan, Italy. [Baccarelli, Andrea A.; Tarantini, Letizia; Bollati, Valentina] Univ Milan, Milan, Italy. [Halonen, Jaana] Finnish Inst Occupat Hlth, Kuopio, Finland. [Wright, Robert O.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02215 USA. [Sparrow, David; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Sparrow, David; Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Alexeeff, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr, Boston, MA 02215 USA. EM salexeeff@fas.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Bollati, Valentina/0000-0002-0370-9598 FU National Institute of Environmental Health Sciences [R01 ES015172]; US Department of Veterans Affairs is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Boston, MA; VA Research Career Scientist award FX This research was supported by National Institute of Environmental Health Sciences grant R01 ES015172. The Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Boston, MA. This research was also supported by a VA Research Career Scientist award to D.S. NR 66 TC 17 Z9 19 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2013 VL 42 IS 1 BP 270 EP 280 DI 10.1093/ije/dys220 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 113WE UT WOS:000316699300034 PM 23508416 ER PT J AU Littman, AJ Jacobson, IG Boyko, EJ Powell, TM Smith, TC AF Littman, A. J. Jacobson, I. G. Boyko, E. J. Powell, T. M. Smith, T. C. CA Millennium Cohort Study Team TI Weight change following US military service SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE military veterans; weight gain; prospective; cohort; posttraumatic stress disorder; military deployment ID VETERANS; OBESITY; COHORT; OVERWEIGHT; VALIDITY; BURDEN AB BACKGROUND: Although overweight and obesity are less prevalent among active-duty military personnel compared with similar persons not serving in the military, no such differences have been observed between veterans and non-veterans. OBJECTIVES: To assess the magnitude of weight changes before, concurrent with and following discharge from the military, relative to weight during service, and to determine the demographic, service-related and psychological characteristics associated with clinically important weight gain among those who were discharged from military service during follow-up. METHODS: Eligible Millennium Cohort Study participants (n = 38 686) completed the questionnaires approximately every 3 years (2001, 2004 and 2007) that were used to estimate annual weight changes, as well as the percentage experiencing clinically important weight gain, defined as >= 10%. Analyses were stratified by sex. RESULTS: Weight gain was greatest around the time of discharge from service and in the 3 years before discharge (1.0-1.3 kg per year), while it was nearly half as much during service (0.6-0.7 kg per year) and >= 3 years after service ended (0.7 kg per year). Consequently, 6-year weight gain was over 2 kg greater in those who were discharged compared with those who remained in the military during follow-up (5.7 vs 3.5 kg in men; 6.3 vs 4.0 kg in women). In those who were discharged, younger age, less education, being overweight at baseline, being in the active-duty component (vs Reserve/National Guard) and having experienced deployment with combat exposures (vs non-deployment) were associated with increased risks of clinically important weight gain. CONCLUSIONS: This study provides the first prospectively collected evidence for an increased rate of weight gain around the time of military discharge that may explain previously reported higher rates of obesity in veterans, and identifies characteristics of higher-risk groups. Discharge from military service presents a window of risk and opportunity to prevent unhealthy weight gain in military personnel and veterans. International Journal of Obesity (2013) 37, 244-253; doi:10.1038/ijo.2012.46; published online 10 April 2012 C1 [Littman, A. J.; Boyko, E. J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, A. J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Jacobson, I. G.; Powell, T. M.; Smith, T. C.] USN, Dept Deployment Hlth Res, Hlth Res Ctr, San Diego, CA 92152 USA. RP Littman, AJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst 152E, Seattle Epidemiol Res & Informat Ctr, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM alyson@u.washington.edu FU Henry M Jackson Foundation for the Advancement of Military Medicine, Rockville, MD; VA Rehabilitation Research and Development Career Development Award [6982]; Cooperative Studies Program, Department of Veterans; Puget Sound VA Medical Center; Department of Defense [60002] FX We are indebted to the Millennium Cohort Study participants, without whom these analyses would not be possible. In addition to the authors, the Millennium Cohort Study Team includes Paul J Amoroso, MD; Gary D Gackstetter, MD, from the Analytic Services, Inc., Arlington, VA; Gregory C Gray, MD, MPH, from the College of Public Health and Health Professions, University of Florida, Gainesville, FL; Tomoko Hooper, MD, from the Departments of Preventive Medicine and Biometrics, Uniformed Services University of Health Sciences, Bethesda, MD; James R Riddle, DVM, MPH, from the Air Force Research Laboratory, Wright-Patterson Air Force Base, OH; Margaret AK Ryan, MD, MPH, from Naval Hospital Camp Pendleton, Occupational Health Department; Melissa Bagnell, MPH; Nancy Crum-Cianflone, MD, MPH; Gia Gumbs, MPH; Nisara Granado, MPH, PhD; Jaime Horton; Kelly Jones, MPH; Cynthia LeardMann, MPH; William Lee; Travis Leleu; Michelle Linfesty; Gordon Lynch; Jamie McGrew; Hope McMaster, PhD; Sheila Medina-Torne, MPH; Amanda Pietrucha, MPH; Donald Sandweiss, MD; Amber Seelig, MPH; Beverly Sheppard; Katherine Snell; Steven Speigle; Kari Sausedo, MA; Donald Slymen, PhD; Besa Smith, MPH, PhD; Jennifer Walstrom; Timothy S Wells, DVM, MPH, PhD; Martin White, MPH; James Whitmer; and Charlene Wong, MPH; from the Department of Deployment Health Research, Naval Health Research Center, San Diego, CA. We thank Scott L Seggerman and Greg D Boyd from the Management Information Division, Defense Manpower Data Center, Monterey, CA. Additionally, we thank Michelle LeWark from the Naval Health Research Center. We also thank all the professionals from the US Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, MD. We appreciate the support of the Henry M Jackson Foundation for the Advancement of Military Medicine, Rockville, MD. Dr Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982).; The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Defense, Department of Veterans Affairs or the US Government. This material is the result of work partly supported with resources and the use of facilities from the Cooperative Studies Program, Department of Veterans and the Puget Sound VA Medical Center. This work represents report 0934, supported by the Department of Defense, under work unit no. 60002. This research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research (Protocol NHRC.2000.007). NR 21 TC 12 Z9 12 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2013 VL 37 IS 2 BP 244 EP 253 DI 10.1038/ijo.2012.46 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 117DK UT WOS:000316932100014 PM 22491091 ER PT J AU Winer, L Srinivasan, D Chun, S Lacomis, D Jaffa, M Fagan, A Holtzman, DM Wancewicz, E Bennett, CF Bowser, R Cudkowicz, M Miller, TM AF Winer, Leah Srinivasan, Dushyanth Chun, Seung Lacomis, David Jaffa, Matthew Fagan, Anne Holtzman, David M. Wancewicz, Ed Bennett, C. Frank Bowser, Robert Cudkowicz, Merit Miller, Timothy M. TI SOD1 in Cerebral Spinal Fluid as a Pharmacodynamic Marker for Antisense Oligonucleotide Therapy SO JAMA NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; SUPEROXIDE-DISMUTASE; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; IN-VIVO; ALS; PROTEIN; MODEL; BIOMARKER AB Background: Therapies designed to decrease the level of SOD1 are currently in a clinical trial for patients with superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (ALS). Objective: To determine whether the SOD1 protein in cerebral spinal fluid (CSF) may be a pharmacodynamic marker for antisense oligonucleotide therapy and a disease marker for ALS. Design: Antisense oligonucleotides targeting human SOD1 were administered to rats expressing SOD1(G93A). The human SOD1 protein levels were measured in the rats' brain and CSF samples. In human CSF samples, the following proteins were measured: SOD1, tau, phosphorylated tau, VILIP-1, and YKL-40. Participants: Ninety-three participants with ALS, 88 healthy controls, and 89 controls with a neurological disease (55 with dementia of the Alzheimer type, 19 with multiple sclerosis, and 15 with peripheral neuropathy). Results: Antisense oligonucleotide-treated SOD1(G93A) rats had decreased human SOD1 messenger RNA levels (mean [SD] decrease of 69% [4%]) and decreased protein levels (mean [SD] decrease of 48% [14%]) in the brain. The rats' CSF samples showed a similar decrease in hSOD1 levels (mean [SD] decrease of 42% [14%]). In human CSF samples, the SOD1 levels varied a mean (SD) 7.1% (5.7%) after additional measurements, separated by months, were performed. The CSF SOD1 levels were higher in the participants with ALS (mean [SE] level, 172 [8] ng/mL; P < .05) and the controls with a neurological disease (mean [SE] level, 172 [6] ng/mL; P < .05) than in the healthy controls (mean [SE] level, 134 [4] ng/mL). Elevated CSF SOD1 levels did not correlate with disease characteristics in participants with ALS or controls with dementia of the Alzheimer type, but they did correlate with tau, phosphorylated tau, VILIP-1 and YKL-40 levels in controls with dementia of the Alzheimer type. Conclusions: SOD1 in CSF may be an excellent pharmacodynamic marker for SOD1-lowering therapies because antisense oligonucleotide therapy lowers protein levels in the rat brain and rat CSF samples and because SOD1 levels in CSF samples from humans are stable over time. JAMA Neurol. 2013;70(2):201-207. Published online November 12, 2012. doi:10.1001/jamaneurol.2013.593 C1 [Winer, Leah; Srinivasan, Dushyanth; Chun, Seung; Fagan, Anne; Holtzman, David M.; Miller, Timothy M.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [Lacomis, David] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Bowser, Robert] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Jaffa, Matthew; Cudkowicz, Merit] Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, Boston, MA 02114 USA. [Wancewicz, Ed; Bennett, C. Frank] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Miller, TM (reprint author), Washington Univ, Dept Neurol, 115 Biotech Bldg,660 S Euclid,POB 8111, St Louis, MO 63110 USA. EM millert@neuro.wustl.edu FU National Institute of Aging of the National Institutes of Health [P01 AG03991, P01 AG026276, U01 AG032438]; Hope Center for Neurological Disorders; ALS Association pilot grant; Clinical and Translation Science Award [UL1 RR024992, K08NS074194]; Washington University Knight Alzheimer's Disease Research Center [P50-AG05681, P01-AG03991, P01-AG26276, P30-NS057105]; University of Pittsburgh [RO1 NS061867-01, RC1 NS068179-01] FX Dr Fagan is supported by grants P01 AG03991, P01 AG026276, and U01 AG032438 from the National Institute of Aging of the National Institutes of Health and by the Hope Center for Neurological Disorders. She is a member of the Alzheimer's Disease CSF Biomarker Development Advisory Board for Roche and the US Alzheimer's Disease Advisory Board for Lilly USA. Isis Pharmaceuticals provided the antisense oligonucleotides used in this study.; This work was supported by an ALS Association pilot grant (to Dr Miller) and Clinical and Translation Science Award grants UL1 RR024992 (to Dr Miller) and K08NS074194 (to Dr Miller). The CSF samples were from Northeast ALS Consortium and the Washington University Knight Alzheimer's Disease Research Center (grants P50-AG05681 [to Dr Morris], P01-AG03991 [to Dr Morris], P01-AG26276 [to Dr Morris], and P30-NS057105 [to Dr Holtzman]), the Charles and Joanne Knight Alzheimer's Disease Research Initiative (to Dr Morris), and the University of Pittsburgh (grants RO1 NS061867-01 [to Dr Bowser] and RC1 NS068179-01 [to Dr Bowser]) NR 29 TC 27 Z9 27 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD FEB PY 2013 VL 70 IS 2 BP 201 EP 207 DI 10.1001/jamaneurol.2013.593 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 115GT UT WOS:000316801300007 PM 23147550 ER PT J AU Tsuang, D Leverenz, JB Lopez, OL Hamilton, RL Bennett, DA Schneider, JA Buchman, AS Larson, EB Crane, PK Kaye, JA Kramer, P Woltjer, R Trojanowski, JQ Weintraub, D Chen-Plotkin, AS Irwin, DJ Rick, J Schellenberg, GD Watson, GS Kukull, W Nelson, PT Jicha, GA Neltner, JH Galasko, D Masliah, E Quinn, JF Chung, KA Yearout, D Mata, IF Wan, JY Edwards, KL Montine, TJ Zabetian, CP AF Tsuang, Debby Leverenz, James B. Lopez, Oscar L. Hamilton, Ronald L. Bennett, David A. Schneider, Julie A. Buchman, Aron S. Larson, Eric B. Crane, Paul K. Kaye, Jeffrey A. Kramer, Patricia Woltjer, Randy Trojanowski, John Q. Weintraub, Daniel Chen-Plotkin, Alice S. Irwin, David J. Rick, Jacqueline Schellenberg, Gerard D. Watson, G. Stennis Kukull, Walter Nelson, Peter T. Jicha, Gregory A. Neltner, Janna H. Galasko, Doug Masliah, Eliezer Quinn, Joseph F. Chung, Kathryn A. Yearout, Dora Mata, Ignacio F. Wan, Jia Y. Edwards, Karen L. Montine, Thomas J. Zabetian, Cyrus P. TI APOE epsilon 4 Increases Risk for Dementia in Pure Synucleinopathies SO JAMA NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LEWY BODIES; COGNITIVE DECLINE; BODY; ALLELE; ASSOCIATION; METAANALYSIS; CONSORTIUM AB Objective: To test for an association between the apolipoprotein E (APOE) epsilon 4 allele and dementias with synucleinopathy. Design: Genetic case-control association study. Setting: Academic research. Patients: Autopsied subjects were classified into 5 categories: dementia with high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body disease (LBD) NCs (AD group; n = 244), dementia with LBDNCs and high-level ADNCs (LBD-AD group; n = 224), dementia with LBDNCs and no or low levels of ADNCs (pure DLB [pDLB] group; n = 91), Parkinson disease dementia (PDD) with no or low levels of ADNCs (n = 81), and control group (n = 269). Main Outcome Measure: The APOE allele frequencies. Results: The APOE e4 allele frequency was significantly higher in the AD (38.1%), LBD-AD (40.6%), pDLB (31.9%), and PDD (19.1%) groups compared with the control group (7.2%; overall chi(2)(4) = 185.25; P = 5.56 X 10(-39)), and it was higher in the pDLB group than the PDD group (P = . 01). In an age-adjusted and sex-adjusted dominant model, epsilon 4 was strongly associated with AD (odds ratio, 9.9; 95% CI, 6.4-15.3), LBD-AD (odds ratio, 12.6; 95% CI, 8.1-19.8), pDLB (odds ratio, 6.1; 95% CI, 3.5-10.5), and PDD (odds ratio, 3.1; 95% CI, 1.7-5.6). Conclusions: The APOE epsilon 4 allele is a strong risk factor across the LBD spectrum and occurs at an increased frequency in pDLB relative to PDD. This suggests that epsilon 4 increases the likelihood of presenting with dementia in the context of a pure synucleinopathy. The elevated epsilon 4 frequency in the pDLB and PDD groups, in which the overall brain neuritic plaque burden was low, indicates that apoE might contribute to neurodegeneration through mechanisms unrelated to amyloid processing. JAMA Neurol. 2013;70(2):223-228. Published online November 19, 2012. doi:10.1001/jamaneurol.2013.600 C1 [Tsuang, Debby; Leverenz, James B.; Watson, G. Stennis; Yearout, Dora; Mata, Ignacio F.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Tsuang, Debby; Leverenz, James B.; Watson, G. Stennis] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.; Yearout, Dora; Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Larson, Eric B.; Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kukull, Walter; Wan, Jia Y.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Trojanowski, John Q.; Irwin, David J.; Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Weintraub, Daniel; Chen-Plotkin, Alice S.; Irwin, David J.; Rick, Jacqueline] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bennett, David A.; Buchman, Aron S.] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Dept Pathol, Chicago, IL 60612 USA. [Kaye, Jeffrey A.; Kramer, Patricia; Quinn, Joseph F.; Chung, Kathryn A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Woltjer, Randy] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Quinn, Joseph F.; Chung, Kathryn A.] Portland VA Med Ctr, Portland, OR USA. [Nelson, Peter T.; Neltner, Janna H.] Univ Kentucky, Dept Pathol, Lexington, KY 40506 USA. [Jicha, Gregory A.] Univ Kentucky, Dept Neurol, Lexington, KY 40506 USA. [Galasko, Doug] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Crane, Paul/C-8623-2014; Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU National Institutes of Health [P30 AG008017, P30 AG028383, P30 AG010124, P30 AG010161, P50 NS053488, P50 AG005131, P50 NS062684, P50 AG005136, P50 AG005133, R01 NS048595, R01 NS065070, R01 AG010845, U01 AG006781]; Department of Veterans Affairs [1I01BX000531] FX Dr Schneider's work was funded by grants from the National Institutes of Health.; This work was supported by grant 1I01BX000531 from the Department of Veterans Affairs and grants P30 AG008017, P30 AG028383, P30 AG010124, P30 AG010161, P50 NS053488, P50 AG005131, P50 NS062684, P50 AG005136, P50 AG005133, R01 NS048595, R01 NS065070, R01 AG010845, and U01 AG006781 from the National Institutes of Health. NR 37 TC 60 Z9 61 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD FEB PY 2013 VL 70 IS 2 BP 223 EP 228 DI 10.1001/jamaneurol.2013.600 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 115GT UT WOS:000316801300010 PM 23407718 ER PT J AU Ziegler, DA Wonderlick, JS Ashourian, P Hansen, LA Young, JC Murphy, AJ Koppuzha, CK Growdon, JH Corkin, S AF Ziegler, David A. Wonderlick, Julien S. Ashourian, Paymon Hansen, Leslie A. Young, Jeremy C. Murphy, Alex J. Koppuzha, Cecily K. Growdon, John H. Corkin, Suzanne TI Substantia Nigra Volume Loss Before Basal Forebrain Degeneration in Early Parkinson Disease SO JAMA NEUROLOGY LA English DT Article ID COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NUCLEUS BASALIS; MR FINDINGS; SPIN-ECHO; INNOMINATA; BRAIN; ACETYLCHOLINESTERASE; PATHOGENESIS; PATHOLOGY AB Objective: To test the hypothesis that degeneration of the substantia nigra pars compacta (SNc) precedes that of the cholinergic basal forebrain (BF) in Parkinson disease (PD) using new multispectral structural magnetic resonance (MR) imaging tools to measure the volumes of the SNc and BF. Design: Matched case-control study. Setting: The Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), and the Massachusetts General Hospital/MIT Morris Udall Center of Excellence in Parkinson Disease Research. Patients: Participants included 29 patients with PD (Hoehn and Yahr [H&Y] stages 1-3) and 27 matched healthy control subjects. Main Outcome Measures: We acquired multiecho T1-weighted, multiecho proton density, T2-weighted, and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences from each participant. For the SNc, we created a weighted mean of the multiple echoes, yielding a single volume with a high ratio of contrast to noise. We visualized the BF using T2-weighted FLAIR images. For each participant, we manually labeled the 2 structures and calculated their volumes. Results: Relative to the controls, 13 patients with H&Y stage 1 PD had significantly decreased SNc volumes. Sixteen patients with H&Y stage 2 or 3 PD showed little additional volume loss. In contrast, the BF volume loss occurred later in the disease, with a significant decrease apparent in patients having H&Y stage 2 or 3 PD compared with the controls and the patients having H&Y stage 1 PD. The latter group did not differ significantly from the controls. Conclusion: Our results support the proposed neuropathological trajectory in PD and establish novel multispectral methods as MR imaging biomarkers for tracking the degeneration of the SNc and BF. JAMA Neurol. 2013;70(2):241-247. Published online November 26, 2012. doi:10.1001/jamaneurol.2013.597- C1 [Ziegler, David A.; Wonderlick, Julien S.; Ashourian, Paymon; Hansen, Leslie A.; Young, Jeremy C.; Murphy, Alex J.; Koppuzha, Cecily K.; Corkin, Suzanne] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Growdon, John H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Growdon, John H.] Massachusetts Gen Hosp, Morris Udall Ctr Excellence Parkinson Dis Res, Boston, MA 02114 USA. RP Ziegler, DA (reprint author), MIT, Dept Brain & Cognit Sci, 43 Vassar St,Room 46-5121, Cambridge, MA 02139 USA. EM daz@mit.edu FU National Institutes of Health [AG021525, DA022759-03, GM0007484,, K23-AG22509, T32 GM007484, T32 MH082718, T90 DA022759]; Health Sciences and Technology Martinos Catalyst Fund FX This research was supported by grants AG021525, DA022759-03, GM0007484, K23-AG22509, T32 GM007484, T32 MH082718, and T90 DA022759 from the National Institutes of Health and by the Health Sciences and Technology Martinos Catalyst Fund. The Athinoula A. Martinos Imaging Center at Massachusetts Institute of Technology's McGovern Institute for Brain Research is supported in part by a generous gift from Pat and Lore McGovern. NR 46 TC 20 Z9 21 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD FEB PY 2013 VL 70 IS 2 BP 241 EP 247 DI 10.1001/jamaneurol.2013.597 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 115GT UT WOS:000316801300013 PM 23183921 ER PT J AU Gabrielian, A MacCumber, MM Kukuyev, A Mitsuyasu, R Holland, GN Sarraf, D AF Gabrielian, Anna MacCumber, Mathew M. Kukuyev, Alla Mitsuyasu, Ronald Holland, Gary N. Sarraf, David TI Didanosine-Associated Retinal Toxicity in Adults Infected With Human Immunodeficiency Virus SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID ZIDOVUDINE; THERAPY C1 [Gabrielian, Anna; MacCumber, Mathew M.] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA. [Kukuyev, Alla; Holland, Gary N.] Univ Calif Los Angeles, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. [Kukuyev, Alla; Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Mitsuyasu, Ronald] Univ Calif Los Angeles, Ctr Clin AIDS Res & Educ, Los Angeles, CA 90095 USA. [Sarraf, David] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu OI Kukuyev, Alla/0000-0003-3472-6523 NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2013 VL 131 IS 2 BP 255 EP 259 PG 6 WC Ophthalmology SC Ophthalmology GA 113RB UT WOS:000316684400029 PM 23411900 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Willett, WC AF Berson, Eliot L. Rosner, Bernard Sandberg, Michael A. Weigel-DiFranco, Carol Willett, Walter C. TI omega-3 Intake in Patients With Retinitis Pigmentosa Receiving Vitamin A reply SO JAMA OPHTHALMOLOGY LA English DT Letter ID DOCOSAHEXAENOIC ACID; CLINICAL-TRIAL C1 [Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Berson, EL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2013 VL 131 IS 2 BP 268 EP 268 PG 1 WC Ophthalmology SC Ophthalmology GA 113RB UT WOS:000316684400035 ER PT J AU Thompson, CF Nabili, V Wang, MB AF Thompson, Christopher F. Nabili, Vishad Wang, Marilene B. TI Pathology Quiz Case 2 Diagnosis SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID SOLITARY EXTRAMEDULLARY PLASMACYTOMA; NECK REGION; HEAD C1 [Thompson, Christopher F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Thompson, CF (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD FEB PY 2013 VL 139 IS 2 BP 197 EP 198 DI 10.1001/jamaoto.2013.1280a PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 114HS UT WOS:000316732300016 PM 23429957 ER PT J AU Ginat, DT Schatz, CJ AF Ginat, Daniel T. Schatz, Charles J. TI Imaging of Silastic Cheek Implant Penetration Into the Maxillary Sinus SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article AB Importance: Silastic implants are popular for cosmetic cheek augmentation. We describe the computed tomographic (CT) and magnetic resonance imaging (MRI) findings in 5 cases (4 patients) with penetration of the medial aspect of Silastic cheek implants through the anterior maxillary sinus wall. Observations: Three cases demonstrated associated sinus mucosal thickening, and 3 cases demonstrated infection surrounding the implant. In 3 cases, the implants migrated into the maxillary sinus, and in 1 case the implant also eroded through the nasoantral wall and extended into the nasal cavity. Conclusions and Relevance: Maxillary sinus penetration is a potential complication of Silastic cheek implants. The extent of this complication can be characterized by CT and MRI. JAMA Otolaryngol Head Neck Surg. 2013; 139(2): 199-201 C1 [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ginat, Daniel T.] Harvard Univ, Sch Med, Boston, MA USA. [Schatz, Charles J.] Beverly Tower Wilshire Adv Imaging, Beverly Hills, CA USA. [Schatz, Charles J.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD FEB PY 2013 VL 139 IS 2 BP 199 EP 201 DI 10.1001/jamaoto.2013.1618 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 114HS UT WOS:000316732300017 PM 23429959 ER PT J AU Wen, Y Feng, J Sachs, G AF Wen, Yi Feng, Jing Sachs, George TI Helicobacter pylori 5 ' ureB-sRNA, a cis-Encoded Antisense Small RNA, Negatively Regulates ureAB Expression by Transcription Termination SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 2-COMPONENT SYSTEM; ALLELIC EXCHANGE; ACID ADAPTATION; PEPTIC-ULCER; PH; COLONIZATION; ATTENUATION; MECHANISMS; LEVEL; GENE AB Urease is an essential component of gastric acid acclimation by Helicobacter pylori. The increased level of urease in gastric acidity is due, in part, to acid activation of the two-component system consisting of the membrane sensor HP0165 (ArsS) and its response regulator HP0166 (ArsR), which regulates transcription of the seven genes in two separate operons (ureAB and ureIEFGH) of the urease gene cluster. Recently, we identified a novel cis-encoded antisense small RNA, 5' ureB-sRNA, targeted at the 5' end of ureB, which downregulates ureAB expression by truncation of the ureAB transcript at neutral pH. It is not known whether the truncated transcript is due to transcription termination or processing of the full-length mRNA by codegradation of a ureAB mRNA-sRNA hybrid complex. S1 nuclease mapping assays show that the truncated transcript is due to transcription termination. Further studies using an in vitro transcription assay found that 5' ureB-sRNA promotes premature termination of transcription of ureAB mRNA. These results suggest that the antisense small RNA 5' ureB-sRNA downregulates ureAB expression by enhancing transcription termination 5' of ureB. With this mechanism, a limited amount of 5' ureB-sRNA is sufficient to regulate the relatively high level of ureAB transcript. C1 [Wen, Yi] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Wen, Y (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90095 USA. EM ywen@ucla.edu FU U.S. Veterans Administration; NIH [DK46917, 53462, 58333] FX This work was supported by U.S. Veterans Administration and NIH grants DK46917, 53462, and 58333. NR 44 TC 7 Z9 8 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2013 VL 195 IS 3 BP 444 EP 452 DI 10.1128/JB.01022-12 PG 9 WC Microbiology SC Microbiology GA 117NS UT WOS:000316960800006 PM 23104809 ER PT J AU Yen, YT Cameron, TA Bensing, BA Seepersaud, R Zambryski, PC Sullam, PM AF Yen, Yihfen T. Cameron, Todd A. Bensing, Barbara A. Seepersaud, Ravin Zambryski, Patricia C. Sullam, Paul M. TI Differential Localization of the Streptococcal Accessory Sec Components and Implications for Substrate Export SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BINDING PROTEIN-GSPB; SURFACE GLYCOPROTEIN GSPB; RICH REPEAT GLYCOPROTEIN; SIGNAL PEPTIDE; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; HUMAN PLATELETS; GORDONII; SYSTEM; BIOGENESIS AB The accessory Sec system of Streptococcus gordonii is comprised of SecY2, SecA2, and five proteins (Asp1 through -5) that are required for the export of a serine-rich glycoprotein, GspB. We have previously shown that a number of the Asps interact with GspB, SecA2, or each other. To further define the roles of these Asps in export, we examined their subcellular localization in S. gordonii and in Escherichia coli expressing the streptococcal accessory Sec system. In particular, we assessed how the locations of these accessory Sec proteins were altered by the presence of other components. Using fluorescence microscopy, we found in E. coli that SecA2 localized within multiple foci at the cell membrane, regardless of whether other accessory Sec proteins were expressed. Asp2 alone localized to the cell poles but formed a similar punctate pattern at the membrane when SecA2 was present. Asp1 and Asp3 localized diffusely in the cytosol when expressed alone or with SecA2. However, these proteins redistributed to the membrane in a punctate arrangement when all of the accessory Sec components were present. Cell fractionation studies with S. gordonii further corroborated these microscopy results. Collectively, these findings indicate that Asp1 to -3 are not integral membrane proteins that form structural parts of the translocation channel. Instead, SecA2 serves as a docking site for Asp2, which in turn attracts a complex of Asp1 and Asp3 to the membrane. These protein interactions may be important for the trafficking of GspB to the cell membrane and its subsequent translocation. C1 [Yen, Yihfen T.; Bensing, Barbara A.; Seepersaud, Ravin; Sullam, Paul M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yen, Yihfen T.; Bensing, Barbara A.; Seepersaud, Ravin; Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cameron, Todd A.; Zambryski, Patricia C.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. RP Sullam, PM (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM paul.sullam@ucsf.edu OI Cameron, Todd/0000-0002-6608-6551 FU Department of Veterans Affairs; VA Merit Review program; Northern California Institute for Research and Education; American Heart Association [10POST3010018, 12POST11040013]; National Institutes of Health [R01 AI41513, R01 AI057433]; National Science Foundation [MCB-0343566] FX This work was supported by the Department of Veterans Affairs, the VA Merit Review program, the Northern California Institute for Research and Education, grants 10POST3010018 and 12POST11040013 (to Y.T.Y.) from the American Heart Association, grants R01 AI41513 and R01 AI057433 (to P.M.S.) from the National Institutes of Health, and grant MCB-0343566 (to P.C.Z.) from the National Science Foundation. NR 44 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2013 VL 195 IS 4 BP 682 EP 695 DI 10.1128/JB.01742-12 PG 14 WC Microbiology SC Microbiology GA 117NW UT WOS:000316961200006 PM 23204472 ER PT J AU Chen, LY Reisner, AT Chen, XX Gribok, A Reifman, J AF Chen, Liangyou Reisner, Andrew T. Chen, Xiaoxiao Gribok, Andrei Reifman, Jaques TI Are Standard Diagnostic Test Characteristics Sufficient for the Assessment of Continual Patient Monitoring? SO MEDICAL DECISION MAKING LA English DT Article DE continual patient monitoring; decision-support algorithm; sequential probability ratio test; physiological data ID INTENSIVE-CARE-UNIT; TRAUMA PATIENTS; PREHOSPITAL HYPOTENSION; EMERGENCY-DEPARTMENT; SCORING SYSTEMS; FALSE ALARMS; VITAL SIGN; MORTALITY; EPIDEMIOLOGY; PROBABILITY AB Background. For diagnostic processes involving continual measurements from a single patient, conventional test characteristics, such as sensitivity and specificity, do not consider decision consistency, which might be a distinct, clinically relevant test characteristic. Objective. The authors investigated the performance of a decision-support classifier for the diagnosis of traumatic injury with blood loss, implemented with three different data-processing methods. For each method, they computed standard diagnostic test characteristics and novel metrics related to decision consistency and latency. Setting. Prehospital air ambulance transport. Patients. A total of 557 trauma patients. Design. Continually monitored vital-sign data from 279 patients (50%) were randomly selected for classifier development, and the remaining were used for testing. Three data-processing methods were evaluated over 16 min of patient monitoring: a 2-min moving window, time averaging, and postprocessing with the sequential probability ratio test (SPRT). Measurements. Sensitivity and specificity were computed. Consistency was quantified through cumulative counts of decision changes over time and the fraction of patients affected by false alarms. Latency was evaluated by the fraction of patients without a decision. Results. All 3 methods showed very similar final sensitivities and specificities. Yet, there were significant differences in terms of the fraction of patients affected by false alarms, decision changes through time, and latency. For instance, use of the SPRT led to a 75% reduction in the number of decision changes and a 36% reduction in the number of patients affected by false alarms, at the expense of 3% unresolved final decisions. Conclusion. The proposed metrics of decision consistency and decision latency provided additional information beyond what could be obtained from test sensitivity and specificity and are likely to be clinically relevant in some applications involving temporal decision making. C1 [Chen, Liangyou; Reisner, Andrew T.; Chen, Xiaoxiao; Gribok, Andrei; Reifman, Jaques] Telemed & Adv Technol Res Ctr TATRC, DoD Biotechnol HPC Software Applicat Inst BHSAI, Ft Detrick, MD USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Reifman, J (reprint author), ATTN MCMR TT, TATRC, BHSAI, 504 Scott St, Ft Detrick, MD 21702 USA. EM jaques.reifman@us.army.mil FU Combat Casualty Care Research Area Directorate of the USAMRMC, Fort Detrick, MD FX Received 10 August 2011 from DoD Biotechnology HPC Software Applications Institute (BHSAI), Telemedicine and Advanced Technology Research Center (TATRC), Fort Detrick, MD (LC, ATR, XC, AG, JR), and Massachusetts General Hospital Department of Emergency Medicine, Boston, MA (ATR). This work was performed at BHSAI, TATRC, US Army Medical Research and Materiel Command (USAMRMC), Fort Detrick, MD 21702. This work was partially supported by the Combat Casualty Care Research Area Directorate of the USAMRMC, Fort Detrick, MD. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The following author is employed by the sponsor: Jaques Reifman is a U.S. Department of the Army Senior Research Scientist. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army or of the U.S. Department of Defense. This article has been approved for public release with unlimited distribution. Revision accepted for publication 24 March 2012. NR 36 TC 5 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD FEB PY 2013 VL 33 IS 2 BP 225 EP 234 DI 10.1177/0272989X12451059 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 113QZ UT WOS:000316684200010 PM 22753421 ER PT J AU Thurber, GM Yang, KS Reiner, T Kohler, RH Sorger, P Mitchison, T Weissleder, R AF Thurber, Greg M. Yang, Katy S. Reiner, Thomas Kohler, Rainer H. Sorger, Peter Mitchison, Tim Weissleder, Ralph TI Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo SO NATURE COMMUNICATIONS LA English DT Article ID OPEN-LABEL; CANCER; INHIBITOR; KINASE; TUMORS; MOUSE; OLAPARIB; MODELS; PARP; PENETRATION AB Pharmacokinetic analysis at the organ level provides insight into how drugs distribute throughout the body, but cannot explain how drugs work at the cellular level. Here we demonstrate in vivo single-cell pharmacokinetic imaging of PARP-1 inhibitors and model drug behaviour under varying conditions. We visualize intracellular kinetics of the PARP-1 inhibitor distribution in real time, showing that PARP-1 inhibitors reach their cellular target compartment, the nucleus, within minutes in vivo both in cancer and normal cells in various cancer models. We also use these data to validate predictive finite element modelling. Our theoretical and experimental data indicate that tumour cells are exposed to sufficiently high PARP-1 inhibitor concentrations in vivo and suggest that drug inefficiency is likely related to proteomic heterogeneity or insensitivity of cancer cells to DNA-repair inhibition. This suggests that single-cell pharmacokinetic imaging and derived modelling improve our understanding of drug action at single-cell resolution in vivo. C1 [Thurber, Greg M.; Yang, Katy S.; Reiner, Thomas; Kohler, Rainer H.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Reiner, Thomas] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Sorger, Peter; Mitchison, Tim; Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480; Thurber, Greg/0000-0001-7570-2080 FU [1R01CA164448]; [PO1CA139980]; [P50CA086355]; [K01DK093766]; [T32 CA079443] FX We thank Yoshiko Iwamoto for expert histopathological analysis, Dr Claudio Vinegoni for intravital imaging, Dr Michael Birrer for cell lines, Dr Gaudenz Danuser for many helpful discussions, Drs Mikael Pittet, John Higgins, Yvonna Fisher-Jeffes, Filip Swirski and Matthias Nahrendorf for critical review, and Edmund Keliher for help with NMR analysis. The work was funded in parts by 1R01CA164448 (R. W., P. S., T. M.), PO1CA139980 (T. M., P. S., R. W.) and P50CA086355 (R. W.). G. T. was supported by K01DK093766. K.Y. was supported by T32 CA079443. NR 52 TC 57 Z9 57 U1 5 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD FEB PY 2013 VL 4 AR 1504 DI 10.1038/ncomms2506 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112TL UT WOS:000316616400074 PM 23422672 ER PT J AU Spindler, MA Galifianakis, NB Wilkinson, JR Duda, JE AF Spindler, Meredith A. Galifianakis, Nicholas B. Wilkinson, Jayne R. Duda, John E. TI Globus pallidus interna deep brain stimulation for tardive dyskinesia: Case report and review of the literature SO PARKINSONISM & RELATED DISORDERS LA English DT Review DE Tardive dyskinesia; Tardive dystonia; Deep brain stimulation; Pallidal stimulation; Globus pallidus ID SECONDARY DYSTONIA; PARKINSONS-DISEASE; PATHOPHYSIOLOGY; MECHANISMS; NEURONS; HYPOTHESIS; OUTCOMES; PATIENT; MOOD AB Tardive dyskinesia (TD) can be a disabling condition and is frequently refractory to medical therapy. Over the past decade there have been many reports of TD patients experiencing significant benefit with deep brain stimulation (DBS) of the globus pallidus interna (GPi). The growing literature on this treatment option for TD consists predominantly of case reports and series. The reported benefit ranges widely, but the majority of cases experienced at least a 50% improvement in symptoms. The anatomical distribution of dyskinesias has not clearly influenced outcome, though fixed postures appear less likely to improve than phasic movements. Onset of benefit can be immediate or take months, and benefit is sustained in most cases, for at least 6 months and up to several years. A wide variety of voltages, frequencies, and pulse widths have demonstrated efficacy. A small number of reports which examined psychiatric symptoms before and after surgery did not find any decline, and in some cases revealed improvement in mood. However, these overall positive results should be interpreted with caution, as the majority of reports lacked blinded assessments, control groups, or standardized therapy parameters. Finally, we present an illustrative case of refractory tardive dyskinesia treated with GPi-DBS with 5 years of follow-up and 4 accompanying video segments. Published by Elsevier Ltd. C1 [Spindler, Meredith A.; Wilkinson, Jayne R.; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19104 USA. [Spindler, Meredith A.; Wilkinson, Jayne R.; Duda, John E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Galifianakis, Nicholas B.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA. RP Duda, JE (reprint author), Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM John.duda@va.gov NR 45 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD FEB PY 2013 VL 19 IS 2 BP 141 EP 147 DI 10.1016/j.parkreldis.2012.09.016 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000316829000001 PM 23099106 ER PT J AU Barry, W St Andre, JR Evans, CT Sabharwal, S Miskevics, S Weaver, FM Smith, BM AF Barry, W. St Andre, J. R. Evans, C. T. Sabharwal, S. Miskevics, S. Weaver, F. M. Smith, B. M. TI Hypertension and antihypertensive treatment in veterans with spinal cord injury and disorders SO SPINAL CORD LA English DT Article DE spinal cord injury; hypertension; blood pressure; antihypertensive; cardiovascular disease; veterans ID CARDIOVASCULAR-DISEASE RISK; CORONARY-HEART-DISEASE; HIGH BLOOD-PRESSURE; PREVALENCE; PREVENTION; MORTALITY; IMPACT AB Hypertension (HTN) is an important risk factor for cardiovascular disease, a major cause of morbidity and mortality among people with spinal cord injury and disorders (SCI/D). Our study examined prevalence, associated factors, and pharmacological treatment of HTN in Veterans with SCI/D compared with a matched control group. Methods: A retrospective review was conducted of Veterans with traumatic SCI/D (TSCI/D; n=6672), non-traumatic SCI/D (NTSCI/D; n=3566) and a matched, non-injured cohort. Results: Over half of patients with TSCI/D (56.6%) had HTN, compared with 68.4% of matched controls (P<0.001). Paraplegic and tetraplegic Veterans with TSCI/D had significantly lower odds of having a HTN diagnosis compared with control (odds ratios (OR) 0.84 (0.77-0.91); OR=0.38 (0.35-0.42)). About 71.8% of patients with NTSCI/D had HTN compared with 72.3% of matched controls (P>0.05). Paraplegic and tetraplegic Veterans with NTSCI/D did not have significantly different odds of a HTN diagnosis compared with control (OR 0.92 (0.79-1.05); OR 0.85 (0.71-1.01)). Adjusted analysis indicates that Veterans with tetraplegia and HTN were less likely to receive antihypertensive therapy (TSCI/D, OR 0.62 (0.53-0.71); NTSCI/D, OR 0.81 (0.66-0.99)). Conclusion: HTN appears to be more prevalent in SCI/D Veterans than previously reported. TSCI/D Veterans have a significantly lower prevalence of HTN whereas NTSCI/D Veterans have a comparable prevalence of HTN to those without SCI/D. The level of injury (tetraplegia vs paraplegia) has a large impact on the prevalence of HTN in the traumatic cohort. Subsequent antihypertensive therapy is used less in both TSCI/D and NTSCI/D Veterans with tetraplegia and more in TSCI/D Veterans with paraplegia. Spinal Cord (2013) 51, 109-115; doi:10.1038/sc.2012.122; published online 13 November 2012 C1 [Barry, W.; Evans, C. T.; Miskevics, S.; Weaver, F. M.; Smith, B. M.] Edward Hines Jr VA Hosp, Dept Vet Affairs VA, Ctr Management Complex Chron Care CMC3, Spinal Cord Injury Qual Enhancement Res Initiat S, Hines, IL USA. [Barry, W.; Weaver, F. M.; Smith, B. M.] Loyola Univ Chicago, Med Ctr, Stritch Sch Med, Loyola Univ, Maywood, IL 60153 USA. [St Andre, J. R.] Hlth Res & Educ Trust, Chicago, IL USA. [Evans, C. T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Sabharwal, S.] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Sabharwal, S.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. RP Barry, W (reprint author), Loyola Univ Chicago, Med Ctr, Stritch Sch Med, Loyola Univ, 2160 South 1st Ave,SSOM DePorres 315, Maywood, IL 60153 USA. FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the Department of Veterans Affairs Spinal Cord Injury Quality Enhancement Research Initiative (SCI QUERI); PVA Research Foundation [2618] FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the Department of Veterans Affairs Spinal Cord Injury Quality Enhancement Research Initiative (SCI QUERI) and by grant # 2618 from the PVA Research Foundation. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 20 TC 4 Z9 4 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD FEB PY 2013 VL 51 IS 2 BP 109 EP 115 DI 10.1038/sc.2012.122 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 114DG UT WOS:000316720500006 PM 23147130 ER PT J AU Liu, G Chen, YH Kolesar, J Huang, W DiPaola, R Pins, M Carducci, M Stein, M Bubley, GJ Wilding, G AF Liu, Glenn Chen, Yu-Hui Kolesar, Jill Huang, Wei DiPaola, Robert Pins, Michael Carducci, Michael Stein, Mark Bubley, Glenn J. Wilding, George TI Eastern Cooperative Oncology Group Phase II Trial of lapatinib in men with biochemically relapsed, androgen dependent prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Epidermal growth factor receptor; Tyrosine kinase inhibitors; Clinical trial ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; RADICAL PROSTATECTOMY; CLINICAL-TRIALS; BREAST-CANCER; WORKING GROUP; ACTIVATION; GEFITINIB; RECOMMENDATIONS; TRASTUZUMAB AB Purpose: Activation of the epidermal growth factor pathway is important in prostate cancer development and the transcription of androgen receptor regulated genes. This study evaluated the potential activity of lapatinib in men with biochemically-relapsed androgen-dependent (stage DO) prostate cancer. Patients and methods: Patients with a rising PSA after primary therapy for prostate cancer were enrolled. A PSA doubling time (PSADT) <12 months was required. Lapatinib was administered at 1,500 mg orally daily. Outcome measures were changes in PSA kinetics. Primary tumor blocks were obtained and assessed for EGFR expression, EGFR Q787Q polymorphism, and Kras 38 mutational status. Results: Forty-nine patients were enrolled (14 ineligible), resulting in 35 patients for analysis. No PSA response was observed; best response was stable disease (n = 28, 80.0%). Pretreatment average slope was 0.19 log (PSA)/month (PSADT = 3.70 months), in contrast to on-treatment average slope of 0.13 log (PSA)/month (PSADT = 5.44 months) using linear mixed effects models (P = 0.006). Median progression-free survival (PFS) was 17.4 months for the high EGFR group and 6.0 months for the low EGER group (P = 0.50). Patients with Kras 38 mutation had shorter PFS than those without Kras 38 mutation (P = 0.09). Conclusion: Although no PSA responses (primary endpoint) was observed, lapatinib may have biologic activity in men with stage DO prostate cancer as evidenced by a decrease in PSA slope in this non-randomized study. Additional trials assessing the role of EGFR overexpression and Kras wild type status in prostate cancer should be investigated. (C) 2013 Elsevier Inc. All rights reserved. C1 [Liu, Glenn; Kolesar, Jill; Huang, Wei; Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [DiPaola, Robert; Stein, Mark] Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Pins, Michael] Univ Illinois, Coll Med, Chicago, IL 60612 USA. [Carducci, Michael] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Liu, G (reprint author), Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA. EM gxl@medicine.wisc.edu FU Frontier Science and Technology Research [UWMO33JK-00]; Public Health Service [CA23318, CA66636, CA21115, CA21076, CA107868, CA16116, CA80775]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Research Support: UWMO33JK-00, Frontier Science and Technology Research. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service grants CA23318, CA66636, CA21115, CA21076, CA107868, CA16116, CA80775, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 38 TC 7 Z9 7 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD FEB PY 2013 VL 31 IS 2 BP 211 EP 218 DI 10.1016/j.urolonc.2011.01.002 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 114XY UT WOS:000316777500013 PM 21784672 ER PT J AU Levitt, JM Jian, WG Lerner, SP Sonpavde, G AF Levitt, Jonathan M. Jian, Weiguo Lerner, Seth P. Sonpavde, Guru TI A conventional preclinical schedule of cisplatin is more effective than a metronomic frequent bolus schedule for urothelial carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Cisplatin; Transitional cell carcinoma; Standard; Metronomic ID TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; GEMCITABINE PLUS CISPLATIN; COOPERATIVE-ONCOLOGY-GROUP; METASTATIC BLADDER-CANCER; 5-DAY CONTINUOUS-INFUSION; LONG-TERM-SURVIVAL; RANDOMIZED-TRIAL; BREAST-CANCER; CHEMOTHERAPY AB Objectives: Given the frequent inability to administer a conventional 3-weekly schedule of cisplatin to human subjects with urothelial carcinoma, we evaluated a frequent bolus metronomic schedule in a preclinical system of transitional cell carcinoma (TCC) of the urothelium. We hypothesized that the anti-angiogenic and anti-cell-migratory activity of lower concentrations of cisplatin may confer similar anti-tumor activity and demonstrate less nephrotoxicity than conventional cytotoxic concentrations. Materials and methods: We evaluated the activity of cisplatin in vitro against human urothelial carcinoma (5637) and endothelial cells (human umbilical vein endothelial cells, HUVECs). The MIT assay was employed to assess viability, and flow cytometry with Annexin-FITC labeling was employed to assess apoptosis. Cell migration in monolayer culture was assessed by scratch assay. Murine xenografts (n = 12 per group) bearing measurable subcutaneous tumors of 5637 cells were administered either no therapy, cisplatin 2 mg/kg/3 days a week (metronomic) or 6 mg/kg/ once a week (standard) intraperitoneal (i.p.) for 4 weeks. Blood was collected from 5 mice per group at baseline and at the end of therapy to measure changes in serum creatinine. Results: Significant antiproliferative activity, but poor pro-apoptotic activity, was observed against 5637 urothelial carcinoma cells in vitro by MIT assay with cisplatin at concentrations lower than those attainable in vivo. Anti-proliferative activity against HUVECs required higher concentrations than attainable in vivo. Anti-migratory activity was observed against 5637 and HUVECs at earlier time points and with concentrations lower than anti-proliferative concentrations. In murine 5637 xenografts, standard cisplatin was significantly better at inhibiting tumor growth than the no treatment control (P = 0.005), while metronomic therapy was not better than control (P = 0.22). Standard cisplatin was also significantly nephrotoxic (P = 0.016), while metronomic cisplatin (P = 0.374) or no therapy (P = 0.178) did not demonstrate significant nephrotoxicity compared with baseline. Conclusions: Cisplatin exhibited anti-cell-migratory activity against urothelial carcinoma and endothelial cells at lower than cytotoxic concentrations. However, a standard preclinical schedule was better than control in vivo for inhibiting tumor growth, while a metronomic schedule was not better. Despite the lower nephrotoxicity of the metronomic schedule, its lower anti-tumor activity suggests that a standard clinical schedule of cisplatin should not be routinely substituted by a split schedule without definitive clinical data. (C) 2013 Elsevier Inc. All rights reserved. C1 [Levitt, Jonathan M.; Jian, Weiguo; Lerner, Seth P.; Sonpavde, Guru] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Levitt, Jonathan M.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Sonpavde, Guru] Texas Oncol Canc Ctr, Webster, TX 77598 USA. [Sonpavde, Guru] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. RP Sonpavde, G (reprint author), Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. EM gurus@bcm.edu NR 32 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD FEB PY 2013 VL 31 IS 2 BP 234 EP 240 DI 10.1016/j.urolonc.2010.11.004 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 114XY UT WOS:000316777500016 PM 21723160 ER PT J AU Sonnenberg, A Boardman, CR AF Sonnenberg, Amnon Boardman, Charles R. TI Costs of Fear SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID AMERICAN-SURGEONS; PRACTICE PATTERNS C1 [Sonnenberg, Amnon; Boardman, Charles R.] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon; Boardman, Charles R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 13 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2013 VL 108 IS 2 BP 173 EP 175 DI 10.1038/ajg.2012.192 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112NZ UT WOS:000316600300003 PM 23381065 ER PT J AU Sonnenberg, A Genta, RM AF Sonnenberg, Amnon Genta, Robert M. TI Helicobacter pylori is a Risk Factor for Colonic Neoplasms SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLORECTAL-CANCER RISK; INTESTINAL METAPLASIA; GASTROINTESTINAL-TRACT; GASTRITIS; INFECTION; DISEASE; IMMUNOHISTOCHEMISTRY; CLASSIFICATION; METAANALYSIS; PATHOLOGY AB OBJECTIVES: It has been suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of adenomatous polyps and adenocarcinoma of the colon. Our aim was to study the association between H. pylori-positive gastritis and the occurrence of any colonic neoplasm. METHODS: From a computerized database of surgical pathology reports, we selected 156,000 subjects who underwent colonoscopy and esophago-gastro-duodenoscopy with biopsy results from both procedures. RESULTS: Compared with normal gastric mucosa, H. pylori gastritis occurred more frequently among patients with hyperplastic polyps (OR = 1.24, 95 % CI: 1.18-1.30), adenomatous polyps (1.52, 1.46-1.57), advanced adenomas (1.80, 1.69-1.92), villous adenomas or adenomas with high-grade dysplasia (1.97, 1.82-2.14), and adenocarcinomas (2.35, 1.98-2.80). Similarly, the strength of the association between H. pylori-positive gastritis and colonic neoplasm increased with size and number of the adenomas. The association between H. pylori gastritis and the occurrence of colonic neoplasm was similar for different locations of the large bowel. Other gastric conditions etiologically associated with H. pylori, such as intestinal metaplasia, adenoma, lymphoma, and adenocarcinoma, were also significantly associated with an increased risk of colonic neoplasm. CONCLUSIONS: Various forms of gastritis related to H. pylori infection confer an increased risk for colonic neoplasm. In the past, when H. pylori infection was more prevalent, its attributable risk to the occurrence of colorectal neoplasm may have been quite substantial. Am J Gastroenterol 2013; 108: 208-215; doi: 10.1038/ajg.2012.407; published online 4 December 2012 C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Miraca Life Sci, Irving, TX USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX Amnon Sonnenberg is supported by a grant from Takeda Pharmaceuticals. Robert M. Genta is employed by Miraca Life Sciences, Irving, TX. NR 32 TC 52 Z9 57 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2013 VL 108 IS 2 BP 208 EP 215 DI 10.1038/ajg.2012.407 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112NZ UT WOS:000316600300009 PM 23208272 ER PT J AU Markman, B Tao, JJ Scaltriti, M AF Markman, Ben Tao, Jessica J. Scaltriti, Maurizio TI PI3K Pathway Inhibitors: Better Not Left Alone SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE PI3K; PIK3CA; PTEN; mTOR; Akt; PI3K inhibitor; therapeutic combination; clinical trial ID VIVO ANTITUMOR-ACTIVITY; POSITIVE BREAST-CANCER; ADVANCED SOLID TUMORS; PHOSPHOINOSITIDE 3-KINASE PATHWAY; RENAL-CELL CARCINOMA; PHOSPHATIDYLINOSITOL 3-KINASE; ESTROGEN DEPRIVATION; KINASE INHIBITOR; PHASE-I; TRASTUZUMAB RESISTANCE AB The PI3K/Akt/mTOR signaling pathway plays a key role in diverse physiologic processes. It is also central to many aspects of the malignant process. Genetic phenomena that lead to constitutive pathway activation are common in human cancer; the most relevant are mutations affecting the catalytic subunit of PI3K and loss of function of the PTEN tumor suppressor. These factors have made this important cascade attractive as a potential target for cancer therapeutics. A host of inhibitors are now in various stages of development that target key nodes within the PI3K pathway. To date, however, the efficacy of these agents has fallen short of expectation, with at least one possible explanation being the presence of feedback loops and cross-talk that exists within and between PI3K and other signaling pathways. Accordingly, enthusiasm is again high as strategies employing therapeutic combinations are gaining pace, with encouraging results documented in both preclinical studies and emerging clinical trials. Here, we review the agents that have reached evaluation in early phase clinical studies of human subjects with cancer, and discuss the rationale for and use of novel drug combinations. C1 [Markman, Ben] So Hlth, Monash Med Ctr, Melbourne, Vic 3165, Australia. [Markman, Ben] Monash Univ, Monash Inst Med Res, Melbourne, Vic 3168, Australia. [Tao, Jessica J.; Scaltriti, Maurizio] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Tao, Jessica J.; Scaltriti, Maurizio] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scaltriti, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, CNY 149,13th St, Charlestown, MA 02129 USA. EM mscaltriti@partners.org NR 114 TC 20 Z9 21 U1 1 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD FEB PY 2013 VL 19 IS 5 BP 895 EP 906 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110NE UT WOS:000316449900008 PM 22973958 ER PT J AU Drakaki, A Hatziapostolou, M Iliopoulos, D AF Drakaki, Alexandra Hatziapostolou, Maria Iliopoulos, Dimitrios TI Therapeutically Targeting MicroRNAs in Liver Cancer SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Liver cancer; microRNAs; networks; delivery technologies ID HUMAN HEPATOCELLULAR-CARCINOMA; HEPATITIS-B-VIRUS; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR GENE; HUMAN HEPATOMA-CELLS; DOWN-REGULATION; C-MYC; PROGNOSTIC-SIGNIFICANCE; REGULATES EXPRESSION; UNITED-STATES AB MicroRNAs are small non-coding RNAs that negatively regulate gene expression through binding on the 3' untranslated region (UTR) of genes. Although microRNAs constitute a small fraction of the human genome, multiple studies have indicated their involvement in the pathogenesis of different types of cancer. Hepatocellular carcinoma (liver) is one of the most aggressive types of cancer with very few therapeutic options. Several studies have revealed that microRNAs are deregulated during liver cancer development and affect central oncogenic and anti-apoptotic liver cancer signaling pathways. Furthermore, the expression levels of specific microRNAs have been identified to be correlated with clinicopathological parameters and treatment responses in liver cancer patients. Here, we review how different epidemiological and liver cancer risk factors, such as the hepatitis B and C viruses, deregulate microRNA-gene circuits in the liver, contributing to liver cancer development. Furthermore, we describe how the most frequently deregulated microRNAs identified in liver cancer patients control their down-stream signaling pathways in liver cancer cells. In addition, we provide examples of microRNAs or microRNA inhibitors that have been used as liver cancer therapeutics and describe novel delivery technologies that could be potentially used in order to optimize the delivery of microRNAs in the liver without having any toxicity or side effects in other major organs. Taken together, there is ample evidence suggesting the deregulation of microRNA-gene circuits in liver, promising that the development of microRNA-based therapeutics could be a clinically viable approach for liver cancer patients. C1 [Drakaki, Alexandra] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA. [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA. RP Iliopoulos, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, 650 Charles E Young Dr South,CHS 33-315, Los Angeles, CA 90095 USA. EM diliopoulos@mednet.ucla.edu RI Hatziapostolou, Maria/N-1820-2015 OI Hatziapostolou, Maria/0000-0003-2493-7028 NR 139 TC 14 Z9 14 U1 1 U2 18 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD FEB PY 2013 VL 19 IS 7 BP 1180 EP 1191 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110NV UT WOS:000316451800002 PM 23092338 ER PT J AU Desai, A Zator, ZA de Silva, P Nguyen, DD Korzenik, J Yajnik, V Ananthakrishnan, AN AF Desai, Amit Zator, Zachary A. de Silva, Punyanganie Nguyen, Deanna D. Korzenik, Joshua Yajnik, Vijay Ananthakrishnan, Ashwin N. TI Older Age Is Associated with Higher Rate of Discontinuation of Anti-TNF Therapy in Patients with Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; ulcerative colitis; age; anti-TNF; infections ID CROHNS-DISEASE; CERTOLIZUMAB PEGOL; MAINTENANCE; INFLIXIMAB; TRIAL; ADALIMUMAB; RISK; IMMUNOMODULATORS; INFECTIONS; REMISSION AB Background: In increasingly aging populations, awareness of outcomes of older patients treated with biologics is becoming more important. However, few studies to date have investigated the safety and durability of anti-tumor necrosis factor (TNF) therapy in this subgroup. Methods: This was a retrospective single-center study with cases comprising all IBD patients who began anti-TNF treatment at age >60 years. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified from medical record review. Our controls consisted of patients younger than age 60 years on anti-TNF treatment and patients >60 years on treatment with immunomodulators. Kaplan-Meier survival estimates were used to calculate the probability of remaining on anti-TNF therapy. Results: We identified a total of 54 IBD patients who initiated anti-TNF therapy over the age of 60 years (mean 73, range 61-97 years). Among these, a total of 38 patients (70%) discontinued anti-TNF therapy after a mean of 24.1 months. At 12 months after initiation, 75% of patients older than age 60 years were still on anti-TNF agents compared to 93% among younger users and 82% among older AZA users (P<0.05). Compared to older AZA users, older anti-TNF users remained more likely to require early therapy cessation (hazard ratio 2.21, 95% confidence interval 1.29-3.78). Conclusions: The IBD population older than age 60 at the time of initiation of anti-TNF therapy is at higher risk for discontinuation of therapy. They may also be particularly vulnerable to infectious complications requiring hospitalization, suggesting the need for careful monitoring during therapy. (Inflamm Bowel Dis 2013; 19: 309-315) C1 [Desai, Amit; Zator, Zachary A.; de Silva, Punyanganie; Nguyen, Deanna D.; Korzenik, Joshua; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [de Silva, Punyanganie; Nguyen, Deanna D.; Korzenik, Joshua; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, 165 Cambridge St,9th Fl, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU Procter and Gamble; Warner Chilcott FX Potential conflict of interest: Joshua Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, CytokinePharma, and receives research support from Procter and Gamble and Warner Chilcott. The other authors declare no conflicts of interest. Author contributions: Amit Desai - study design, data collection, analysis and interpretation of data, drafting of the article, critical revision of the article for important intellectual content; Zachary Zator - study design, data collection, analysis and interpretation of data, drafting of the article, critical revision of the article for important intellectual content; P. de Silva-data collection, analysis and interpretation of data, critical revision of the article for important intellectual content. D. Nguyen - data, collection, critical revision of the article for important intellectual content; V. Yajnik - data, collection, critical revision of the article for important intellectual content; J. Korzenik - data, collection, critical revision of the article for important intellectual content; A. Ananthakrishnan - study design, data collection, analysis and interpretation of data, drafting of the article, critical revision of the article for important intellectual content. NR 28 TC 24 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2013 VL 19 IS 2 BP 309 EP 315 DI 10.1002/ibd.23026 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 110MM UT WOS:000316447300027 PM 22605668 ER PT J AU Lye-Barthel, M Sun, D Jakobs, TC AF Lye-Barthel, Ming Sun, Daniel Jakobs, Tatjana C. TI Morphology of Astrocytes in a Glaucomatous Optic Nerve SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ELEVATED INTRAOCULAR-PRESSURE; RETROGRADE AXOPLASMIC-TRANSPORT; RETINAL GANGLION-CELLS; DBA/2J MICE; AXONAL-TRANSPORT; HEAD; TISSUE; DAMAGE; MOUSE; DEGENERATION AB PURPOSE. To establish the morphologic changes of astrocytes in the glial lamina of glaucomatous mice. METHODS. A strain of mice that expresses GFP in individual astrocytes (hGFAPpr-GFP) was crossed into the DBA/2J strain that develops glaucoma. In the resulting strain (D2.hGFAPpr-GFP) we assessed the severity of glaucoma by staining the retina for neurofilaments and counting the neurons of the retinal ganglion cell layer. We observed the morphology of astrocytes in the glial lamina of the optic nerves. RESULTS. D2.hGFAPpr-GFP mice developed glaucoma in an age-dependent manner. Astrocytes in the glial lamina showed morphologic changes that correlated with the severity of glaucoma. The cells showed thickening of processes from 1.3 +/- 0.28 mu m in nondiseased animals to 1.71 +/- 0.46 mu m in eyes with moderate glaucoma and 2.1 +/- 0.42 mu m in those with severe glaucoma. Their spatial coverage, as determined by their convex polygon area, was reduced in eyes with severe glaucoma. The astrocytes in severely glaucomatous optic nerves also showed simplification of their processes. In 6-month-old mice with no obvious signs of degeneration in the retina, we found astrocytes with appendages growing out of primary astrocyte processes into the axon bundles. This localized hypertrophy of processes was never observed in the hGFAPpr-GFP strain. CONCLUSIONS. Confirming results after optic nerve crush, astrocytes in glaucomatous optic nerves had thickened and simplified processes, and reduced spatial coverage. We also found evidence of localized sprouting of new processes in early stages of the disease, before detectable changes in ganglion cell number. (Invest Ophthalmol Vis Sci. 2013; 54:909-917) DOI: 10.1167/iovs.12-10109 C1 [Lye-Barthel, Ming; Sun, Daniel; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jakobs, TC (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Tatjana_Jakobs@meei.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU NIH Grant [EY019703]; Glaucoma Foundation; American Health Assistance Foundation; Research to Prevent Blindness; Massachusetts Lions Eye Research Fund; [EY14104] FX Supported by NIH Grant EY019703 and by grants from the Glaucoma Foundation and the American Health Assistance Foundation, by the Core Grant EY14104 (to Massachusetts Eye and Ear Infirmary), and by grants from Research to Prevent Blindness and the Massachusetts Lions Eye Research Fund. NR 33 TC 35 Z9 35 U1 2 U2 12 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2013 VL 54 IS 2 BP 909 EP 917 DI 10.1167/iovs.12-10109 PG 9 WC Ophthalmology SC Ophthalmology GA 100BS UT WOS:000315670300001 PM 23322566 ER PT J AU Darabad, RR Suzuki, T Richards, SM Jensen, RV Jakobiec, FA Zakka, FR Liu, SH Sullivan, DA AF Darabad, Raheleh Rahimi Suzuki, Tomo Richards, Stephen M. Jensen, Roderick V. Jakobiec, Frederick A. Zakka, Fouad R. Liu, Shaohui Sullivan, David A. TI Influence of Aromatase Absence on the Gene Expression and Histology of the Mouse Meibomian Gland SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DRY EYE SYNDROME; SEBACEOUS GLAND; SJOGRENS-SYNDROME; KNOCKOUT MOUSE; LIPID PROFILES; SEX STEROIDS; MICROARRAY PLATFORMS; ESTROGEN REPLACEMENT; ANDROGEN DEFICIENCY; GENDER-DIFFERENCES AB PURPOSE. We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice. METHODS. Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays. RESULTS. Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice. CONCLUSIONS. Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland. (Invest Ophthalmol Vis Sci. 2013;54:987-998) DOI:10.1167/iovs.12-10992 C1 [Darabad, Raheleh Rahimi; Suzuki, Tomo; Richards, Stephen M.; Liu, Shaohui; Sullivan, David A.] Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. [Darabad, Raheleh Rahimi; Suzuki, Tomo; Richards, Stephen M.; Jakobiec, Frederick A.; Zakka, Fouad R.; Liu, Shaohui; Sullivan, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Jensen, Roderick V.] Virginia Tech, Dept Biol Sci, Blacksburg, VA USA. [Jakobiec, Frederick A.; Zakka, Fouad R.; Sullivan, David A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu FU National Institutes of Health [R01EY05612]; Margaret S. Sinon Scholar in Ocular Surface Research fund; Allergan, Japan; Bausch Lomb; Japan Eye Bank Association FX Supported by National Institutes of Health Grant R01EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research fund, and postdoctoral fellowship awards from Allergan, Japan, Bausch & Lomb, and the Japan Eye Bank Association. NR 69 TC 6 Z9 6 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2013 VL 54 IS 2 BP 987 EP 998 DI 10.1167/iovs.12-10992 PG 12 WC Ophthalmology SC Ophthalmology GA 100BS UT WOS:000315670300010 PM 23233261 ER PT J AU Liu, J Clermont, AC Gao, BB Feener, EP AF Liu, Jia Clermont, Allen C. Gao, Ben-Bo Feener, Edward P. TI Intraocular Hemorrhage Causes Retinal Vascular Dysfunction via Plasma Kallikrein SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BLOOD-BRAIN-BARRIER; INTRACEREBRAL HEMORRHAGE; DIABETIC-RATS; IN-VIVO; KININ SYSTEM; FACTOR-XII; PERMEABILITY; ACTIVATION; PERICYTES; COL4A1 AB PURPOSE. Retinal hemorrhages occur in a variety of sight-threatening conditions including ocular trauma, high altitude retinopathy, and chronic diseases such as diabetic and hypertensive retinopathies. The goal of this study is to investigate the effects of blood in the vitreous on retinal vascular function in rats. METHODS. Intravitreal injections of autologous blood, plasma kallikrein (PK), bradykinin, and collagenase were performed in Sprague-Dawley and Long-Evans rats. Retinal vascular permeability was measured using vitreous fluorophotometry and Evans blue dye permeation. Leukostasis was measured by fluorescein isothiocyanate-coupled concanavalin A lectin and acridine orange labeling. Retinal hemorrhage was examined on retinal flatmounts. Primary cultures of bovine retinal pericytes were cultured in the presence of 25 nM PK for 24 hours. The pericyte-conditioned medium was collected and the collagen proteome was analyzed by tandem mass spectrometry. RESULTS. Intravitreal injection of autologous blood induced retinal vascular permeability and retinal leukostasis, and these responses were ameliorated by PK inhibition. Intravitreal injections of exogenous PK induced retinal vascular permeability, leukostasis, and retinal hemorrhage. Proteomic analyses showed that PK increased collagen degradation in pericyte-conditioned medium and purified type IV collagen. Intravitreal injection of collagenase mimicked PK's effect on retinal hemorrhage. CONCLUSIONS. Intraocular hemorrhage increases retinal vascular permeability and leukostasis, and these responses are mediated, in part, via PK. Intravitreal injections of either PK or collagenase, but not bradykinin, induce retinal hemorrhage in rats. PK exerts collagenase-like activity that may contribute to blood-retinal barrier dysfunction. (Invest Ophthalmol Vis Sci. 2013;54:1086-1094) DOI:10.1167/iovs.12-10537 C1 [Liu, Jia; Clermont, Allen C.; Gao, Ben-Bo; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Dept Med, Boston, MA 02115 USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU US National Institutes of Health [EY 19029, DK36836]; Juvenile Diabetes Research Foundation (JDRF) [17-2011-251] FX Supported in part by the US National Institutes of Health Grants EY 19029 and DK36836, and Juvenile Diabetes Research Foundation (JDRF) Grant 17-2011-251. NR 48 TC 8 Z9 8 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2013 VL 54 IS 2 BP 1086 EP 1094 DI 10.1167/iovs.12-10537 PG 9 WC Ophthalmology SC Ophthalmology GA 100BS UT WOS:000315670300022 PM 23299478 ER PT J AU Velez, G Weingarden, AR Lei, HT Kazlauskas, A Gao, GP AF Velez, Gisela Weingarden, Alexa R. Lei, Hetian Kazlauskas, Andrius Gao, Guangping TI SU9518 Inhibits Proliferative Vitreoretinopathy in Fibroblast and Genetically Modified Muller Cell-Induced Rabbit Models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GROWTH-FACTOR RECEPTOR; EXPERIMENTAL RETINAL-DETACHMENT; TYROSINE KINASE INHIBITOR; ACIDIC PROTEIN; EXPRESSION; VIMENTIN; ALPHA AB PURPOSE. Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment that can lead to surgical failure and vision loss. Previous studies suggest that a variety of retinal cells, including RPE and Muller glia, may be responsible. Platelet-derived growth factor receptor alpha (PDGFR alpha) has been strongly implicated in the pathogenesis, and found to be intrinsic to the development of PVR in rabbit models. We examine whether SU9518, a tyrosine kinase inhibitor with PDGFR alpha specificity, can inhibit the development of PVR in fibroblast and Muller cell rabbit models of PVR. METHODS. SU9518 was injected in rabbit eyes along with fibroblasts, Muller cells (MIO-M1), or Muller cells transfected to increase their expression of PDGFR alpha (MIO-M1 alpha). Indirect ophthalmoscopy and histopathology were used to assess efficacy and toxicity. RESULTS. SU9518 was an effective inhibitor of PVR in both fibroblast and Muller cell models of PVR. No toxic effects were identified by indirect ophthalmoscopy or histopathology. CONCLUSIONS. SU9518 is an effective and safe inhibitor of PVR in rabbit models, and could potentially be used in humans for the treatment of this and other proliferative diseases of the retina involving fibrosis and gliosis. Further animal studies need to be performed to examine retinal toxicity and sustained delivery mechanisms. (Invest Ophthalmol Vis Sci. 2013; 54: 1392-1397) DOI: 10.1167/iovs.12-10320 C1 [Velez, Gisela] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA 01605 USA. [Velez, Gisela; Gao, Guangping] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA 01605 USA. [Weingarden, Alexa R.; Lei, Hetian; Kazlauskas, Andrius] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Lei, Hetian; Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Velez, G (reprint author), Univ Massachusetts, Sch Med, Dept Ophthalmol, 381 Plantat St,Suite 250, Worcester, MA 01605 USA. EM Gisela.velez@umassmed.edu FU National Eye Institute [K08EY17383] FX Supported by National Eye Institute Grant K08EY17383. NR 24 TC 8 Z9 8 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2013 VL 54 IS 2 BP 1392 EP 1397 DI 10.1167/iovs.12-10320 PG 6 WC Ophthalmology SC Ophthalmology GA 100BS UT WOS:000315670300061 PM 23341018 ER PT J AU Scarcelli, G Kling, S Quijano, E Pineda, R Marcos, S Yun, SH AF Scarcelli, Giuliano Kling, Sabine Quijano, Elena Pineda, Roberto Marcos, Susana Yun, Seok Hyun TI Brillouin Microscopy of Collagen Crosslinking: Noncontact Depth-Dependent Analysis of Corneal Elastic Modulus SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OCULAR RESPONSE ANALYZER; ULTRAVIOLET-A LIGHT; BIOMECHANICAL PROPERTIES; EPITHELIAL DEBRIDEMENT; OPTICAL MICROSCOPY; PROGRESSIVE KERATOCONUS; BENZALKONIUM CHLORIDE; RIBOFLAVIN; EYES; SPECTROSCOPY AB PURPOSE. Corneal collagen crosslinking (CXL) is designed to halt the progression of keratoconus and corneal ectasia by inducing corneal stiffening. However, it currently is difficult to monitor and evaluate CXL outcome objectively due to the lack of suitable methods to characterize corneal mechanical properties. We validated noncontact Brillouin microscopy to quantify corneal mechanical properties before and after CXL. METHODS. CXL was performed on fresh porcine eyes using various presoaking times and light doses, with or without epithelial debridement. From Brillouin maps of corneal elastic modulus, stiffness and average modulus of anterior, middle, and posterior stroma were analyzed. Corneal stiffening index (CSI) was introduced as a metric to compare the mechanical efficacy of a given CXL protocol with respect to the standard protocol (30-minute riboflavin presoak, 3 mW/cm(2) ultraviolet illumination for 30 minutes). RESULTS. Brillouin corneal stiffness increased significantly (P < 0.001) by epi-off and epi-on CXL. The increase of Brillouin modulus was depth-dependent, indicating that anterior stromal stiffening contributes the most to mechanical outcome. The increase of anterior Brillouin modulus was linearly proportional to the light dose (R-2 > 0.98). Compared to the standard epi-off procedure, a typical epi-on procedure resulted in a third of stiffness increase in porcine corneas (CSI = 33). CONCLUSIONS. Brillouin microscopy allowed imaging and quantifying CXL-induced mechanical changes without contact in a depth-dependent manner at high spatial resolution. This technique may be useful to evaluate the mechanical outcomes of CXL procedures, to compare different crosslinking agents, and for real-time monitoring of CXL in clinical and experimental settings. (Invest Ophthalmol Vis Sci. 2013; 54: 1418-1425) DOI:10.1167/iovs.12-11387 C1 [Scarcelli, Giuliano; Quijano, Elena; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA USA. [Scarcelli, Giuliano; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Kling, Sabine; Marcos, Susana] CSIC, Inst Opt, E-28006 Madrid, Spain. [Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Yun, SH (reprint author), 65 Landsdowne St,UP 5, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU Harvard Clinical and Translational Science Center [NIH UL1-RR025758]; American Society for Laser Medicine and Surgery; National Institutes of Health [P41-EB015903]; National Science of Foundation [CBET-0853773]; Spanish Government [FIS2008-02065, FIS2011-25637]; European Research Council [ERC-AdG-294099] FX Supported by the Harvard Clinical and Translational Science Center (NIH UL1-RR025758), American Society for Laser Medicine and Surgery, National Institutes of Health (P41-EB015903), National Science of Foundation (CBET-0853773), Spanish Government (FIS2008-02065, FIS2011-25637), and the European Research Council (ERC-AdG-294099). NR 47 TC 72 Z9 73 U1 0 U2 30 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2013 VL 54 IS 2 BP 1418 EP 1425 DI 10.1167/iovs.12-11387 PG 8 WC Ophthalmology SC Ophthalmology GA 100BS UT WOS:000315670300065 PM 23361513 ER PT J AU Ahluwalia, SK Peng, R Aloe, C Shreffler, WG Krevans, M Hagberg, KA Thorne, PS Matsui, E AF Ahluwalia, Sharon K. Peng, Roger Aloe, Charles Shreffler, Wayne G. Krevans, Mary Hagberg, Karol A. Thorne, Peter S. Matsui, Elizabeth TI Endotoxin Exposure May Modify the Relationship Between Mouse Allergen Exposure and Incident Sensitization to Mouse SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Ahluwalia, Sharon K.; Aloe, Charles; Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Peng, Roger] Johns Hopkins Univ, Baltimore, MD USA. [Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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Phipatanakul, Wanda TI Classroom Fungal Spore Exposure and Asthma Morbidity in Inner-City School Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Baxi, Sachin N.; Petty, Carter R.; Sheehan, William J.; Kopel, Lianne; Kanchongkittiphon, Watcharoot; Gaffin, Jonathan M.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Fu, Chunxia] Harvard Univ, Sch Med, Boston, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. [Rogers, Christine A.; Muilenberg, Michael L.] Univ Massachusetts, Amherst, MA 01003 USA. [Gold, Diane R.] Channing Labs, Boston, MA USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB54 EP AB54 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800197 ER PT J AU Brennan, AK Patil, SU Fleming, J Boyce, JA Stieb, ES Nichols, M Iyengar, RS Permaul, P Walter, JE Hesterberg, P Shreffler, WG AF Brennan, Alisa K. Patil, Sarita U. Fleming, Jude Boyce, Joshua A. Stieb, Elisabeth S. Nichols, Margaux Iyengar, Rajashri Shuba Permaul, Perdita Walter, Jolan E. Hesterberg, Paul Shreffler, Wayne G. TI Outcomes Using a Graded Protocol for Open Food Challenges SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Brennan, Alisa K.; Patil, Sarita U.; Nichols, Margaux; Iyengar, Rajashri Shuba; Walter, Jolan E.; Hesterberg, Paul; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fleming, Jude] Brown Univ, Rhode Isl Hosp, Dept Pediat, Div Asthma & Allergy,Alpert Sch Med, Providence, RI 02903 USA. [Boyce, Joshua A.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Stieb, Elisabeth S.] Massachusetts Gen Hosp, S Weymouth, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. [Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB86 EP AB86 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800313 ER PT J AU Ferzacca, E Alejos, AR Leibowitz, R Pistiner, M Shreffler, WG Sheetz, A AF Ferzacca, Elizabeth Alejos, Alexandra R. Leibowitz, Robert Pistiner, Michael Shreffler, Wayne G. Sheetz, Anne TI Real-Time Surveillance of Epinephrine Administration in Schools Supports the Argument for Stock' Epinephrine Availability SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Ferzacca, Elizabeth] Barnard, Boston, MA USA. [Ferzacca, Elizabeth; Alejos, Alexandra R.; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leibowitz, Robert; Sheetz, Anne] Massachusetts Dept Publ Hlth, Boston, MA USA. [Pistiner, Michael] Harvard Vanguard Med Associates, Boston, MA USA. [Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB219 EP AB219 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800779 ER PT J AU Fleming, J Clark, S Camargo, C Rudders, SA AF Fleming, Jude Clark, Sunday Camargo, Carlos, Jr. Rudders, Susan A. TI Early Treatment of Food-Induced Allergic Reactions with Epinephrine Is Associated with Lower Risk of Hospital Admission SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Fleming, Jude; Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Dept Pediat, Div Asthma & Allergy,Alpert Sch Med, Providence, RI 02903 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB90 EP AB90 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800326 ER PT J AU Greenhawt, MJ Weiss, CC Conte, M Doucet, M Engler, A Camargo, C AF Greenhawt, Matthew J. Weiss, Christopher C. Conte, Marisa Doucet, Marlie Engler, Amy Camargo, Carlos, Jr. TI Racial and Ethnic Disparity in Food Allergy in the United States: A Systematic Review SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Greenhawt, Matthew J.] Univ Michigan, Sch Med, Dept Internal Med, Div Allergy & Clin Immunol, Ann Arbor, MI USA. [Weiss, Christopher C.] Global Food Protect Inst, Battle Creek, MI USA. [Conte, Marisa] Univ Michigan, Taubman Hlth Sci Lib, Ann Arbor, MI 48109 USA. [Doucet, Marlie] Ctr Dis Control & Prevent, Div Adolescent & Sch Hlth, Atlanta, GA USA. [Engler, Amy] Stanford Univ, EHuman Biol Dept, Palo Alto, CA 94304 USA. [Camargo, Carlos, Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB58 EP AB58 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800208 ER PT J AU Guana, A Simons, FERR Wang, S Camargo, C AF Guana, Adriana Simons, F. Estelle R. R. Wang, Sheldon Camargo, Carlos, Jr. TI Auvi-Q Versus Epipen: Preferences of Adults, Caregivers, and Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Simons, F. Estelle R. R.] Univ Manitoba, Winnipeg, MB, Canada. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB213 EP AB213 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800760 ER PT J AU Guyer, AC Conroy, M Carlos-Camargo Jr Long, AD Banerji, A AF Guyer, Autumn Chandler Conroy, Michelle Carlos-Camargo, Jr. Long, Aidan Banerji, Aleena TI Comprehensive Allergy Consultation Minimizes Risk of Hypersensitivity Reaction During Subsequent Anesthesia SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Guyer, Autumn Chandler; Conroy, Michelle; Long, Aidan; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Carlos-Camargo, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB176 EP AB176 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800624 ER PT J AU Harper, N Castiblanco, J Rather, C Andrews, C Ramirez, D Jacobs, RL He, WJ Ahuja, S AF Harper, Nathan Castiblanco, John Rather, Cynthia Andrews, Charles Ramirez, Daniel Jacobs, Robert L. He, Weijing Ahuja, Sunil TI RNA-Seq-Derived Whole Genome Transcriptomic Profiling Following Challenge to Mt. Cedar in a Pollen Challenge Chamber Uncover Novel Insights Into Allergic Rhinoconjunctivitis Pathogenesis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Harper, Nathan; Castiblanco, John; He, Weijing; Ahuja, Sunil] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Harper, Nathan; Castiblanco, John; He, Weijing; Ahuja, Sunil] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Rather, Cynthia; Andrews, Charles; Ramirez, Daniel; Jacobs, Robert L.] Biogen Res Chamber, San Antonio, TX USA. RI CASTIBLANCO, JOHN/B-6599-2009 OI CASTIBLANCO, JOHN/0000-0002-7965-9822 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB40 EP AB40 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800147 ER PT J AU He, WJ Carrillo, A Harper, N Jimenez, F Martinez, H Ahuja, S Rather, C Ramirez, D Andrews, C Jacobs, RL Ahuja, S AF He, Weijing Carrillo, Andrew Harper, Nathan Jimenez, Fabio Martinez, Hernan Ahuja, Seema Rather, Cynthia Ramirez, Daniel Andrews, Charles Jacobs, Robert L. Ahuja, Sunil TI Exposure to Juniperus Ashei (Mt. Cedar) Pollen in a Pollen Challenge Chamber Elicits Changes in White Blood Cell Counts and Cytokines in Mountain Cedar Positive and Negative Subjects SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [He, Weijing; Carrillo, Andrew; Harper, Nathan; Jimenez, Fabio; Martinez, Hernan; Ahuja, Seema; Ahuja, Sunil] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [He, Weijing; Carrillo, Andrew; Harper, Nathan; Jimenez, Fabio; Martinez, Hernan; Ahuja, Seema; Ahuja, Sunil] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Rather, Cynthia; Ramirez, Daniel; Andrews, Charles; Jacobs, Robert L.] Biogen Res Chamber, San Antonio, TX USA. 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TI Tolerance of Baked Milk in a Subset of Patients with Cow's Milk-Mediated Eosinophilic Esophagitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Leung, John; Katz, Aubrey J.; Yuan, Qian; Iyengar, Rajashri Shuba; Walter, Jolan E.; Ramakrishna, Jyoti; Hundal, Navneet; Swenson, Theadora; Alejos, Alexandra R.; Shreffler, Wayne G.; Hesterberg, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB181 EP AB181 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800643 ER PT J AU Ling, M Patil, SU Wong, JT AF Ling, Morris Patil, Sarita U. Wong, Johnson T. TI Oxaliplatin Hypersensitivity: Management and Comparison with Carbo/Cisplatin SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Ling, Morris; Patil, Sarita U.; Wong, Johnson T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ling, Morris; Patil, Sarita U.; Wong, Johnson T.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. 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TI Induction of Antigen-Specific B Cells During Peanut Oral Immunotherapy Using Novel Tetramer-Based Approach SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Patil, Sarita U.; Brennan, Alisa K.; Ma, Alex; Moon, James; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kubala, Stephanie] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Shreffler, Wayne G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB86 EP AB86 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800312 ER PT J AU Permaul, P Petty, CR Sheehan, WJ Baxi, SN Gaffin, JM Kopel, LS Kanchongkittiphan, W Bailey, A Fu, CX Gold, DR Phipatanakul, W AF Permaul, Perdita Petty, Carter R. Sheehan, William J. Baxi, Sachin N. Gaffin, Jonathan M. Kopel, Lianne S. Kanchongkittiphan, Watcharoot Bailey, Ann Fu, Chunxia Gold, Diane R. Phipatanakul, Wanda TI Mouse Allergen Exposure in Urban Schools and Its Effect On Childhood Asthma Morbidity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy Immunol, Boston, MA 02114 USA. 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Cedar) and Virginia Live Oak Pollen in a Pollen Challenge Chamber Elicits Similar Symptomology When Compared to Natural Season SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Ramirez, Daniel; Rather, Cynthia; Andrews, Charles; Jacobs, Robert L.] Biogen Res Chamber, San Antonio, TX USA. [Harper, Nathan; Carrillo, Andrew; He, Weijing; Ahuja, Sunil] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Harper, Nathan; Carrillo, Andrew; He, Weijing; Ahuja, Sunil] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB49 EP AB49 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800178 ER PT J AU Rudders, SA Clark, S Wei, WH Camargo, C AF Rudders, Susan A. Clark, Sunday Wei, Wenhui Camargo, Carlos, Jr. TI A Retrospective Study of Drug-Induced Anaphylaxis Treated in the Emergency Department (ED) or Hospital: Patients' Characteristics and Their Receipt of Preventive Care SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Alpert Sch Med, Div Asthma & Allergy,Dept Pediat, Providence, RI 02903 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Wei, Wenhui] Sanofi US, Evidence Based Med, Bridgewater, NJ USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB174 EP AB174 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800617 ER PT J AU Ruiter, B Grishina, G Jager, SD Knol, EF Ozias-Akins, P Sampson, HA Shreffler, WG AF Ruiter, Bert Grishina, Galina Jager, Stans den Hartog Knol, Edward F. Ozias-Akins, Peggy Sampson, Hugh A. Shreffler, Wayne G. TI Human Dendritic Cells Stimulated with a Novel Peanut Protein Express High Levels of RALDH2 and Induce RA-Sensitive Genes in Naive T Cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Ruiter, Bert; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grishina, Galina; Sampson, Hugh A.] Mt Sinai Sch Med, New York, NY USA. [Jager, Stans den Hartog; Knol, Edward F.] Univ Med Ctr, Utrecht, Netherlands. [Ozias-Akins, Peggy] Univ Georgia, Tifton, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB127 EP AB127 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800457 ER PT J AU Viswanathan, RK Mathur, SK AF Viswanathan, Ravi K. Mathur, Sameer K. TI Autoimmune Phenotype in Refractory Chronic Urticaria Does Not Affect Response to Omalizumab SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Viswanathan, Ravi K.; Mathur, Sameer K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Viswanathan, Ravi K.; Mathur, Sameer K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB30 EP AB30 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800109 ER PT J AU Wong, JT AF Wong, Johnson T. TI Rapid Outpatient Aspirin Desensitization/Challenge for Urticaria/Angioedema and AERD SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Wong, Johnson T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wong, Johnson T.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Johnson T.] Newton Wellesley Hosp, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB167 EP AB167 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800591 ER PT J AU Abel, BS Shaw, ND Brown, JM Adams, JM Alati, T Martin, KA Pitteloud, N Seminara, SB Plummer, L Pignatelli, D Crowley, WF Welt, CK Hall, JE AF Abel, Brent S. Shaw, Natalie D. Brown, Jenifer M. Adams, Judith M. Alati, Teresa Martin, Kathryn A. Pitteloud, Nelly Seminara, Stephanie B. Plummer, Lacey Pignatelli, Duarte Crowley, William F., Jr. Welt, Corrine K. Hall, Janet E. TI Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; ENDOTHELIAL GROWTH-FACTOR; HUMAN MENSTRUAL-CYCLE; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; PHENOTYPIC SPECTRUM; CHARGE SYNDROME; RECEPTOR MUTATIONS; HUMAN OVARY AB Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. (J Clin Endocrinol Metab 98: E206-E216, 2013) C1 [Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Seminara, Stephanie B.; Plummer, Lacey; Crowley, William F., Jr.; Welt, Corrine K.; Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit,Dept Med, Boston, MA 02114 USA. [Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Seminara, Stephanie B.; Plummer, Lacey; Crowley, William F., Jr.; Welt, Corrine K.; Hall, Janet E.] Harvard Univ, Sch Med, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Shaw, Natalie D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Pitteloud, Nelly] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Pignatelli, Duarte] Univ Porto, Hosp San Joao, Fac Med Porto, Dept Endocrinol,Dept Expt Biol, P-4200 Oporto, Portugal. [Pignatelli, Duarte] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, P-4200 Oporto, Portugal. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, 55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI PITTELOUD, Nelly/K-2709-2014; OI Pignatelli, Duarte/0000-0002-5555-7004; Welt, Corrine/0000-0002-8219-5504; Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU Eunice Kennedy Shriver National Institutes of Child Health and Human Development/National Institutes of Health [R01 HD42708]; Specialized Cooperative Centers Program in Reproduction and Infertility Research [U54 HD028138]; National Institutes of Health National Center for Research Resources, General Clinical Research Centers Program [M01-RR-01066]; National Institutes of Health [5F32 HD062315]; Scholars in Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center] [UL1RR025758]; Harvard University FX This work was supported by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development/National Institutes of Health through R01 HD42708 and cooperative agreement U54 HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research and M01-RR-01066 National Institutes of Health National Center for Research Resources, General Clinical Research Centers Program. N.D.S. received fellowship support from the National Institutes of Health (Grant 5F32 HD062315) and from the Scholars in Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center (Award UL1RR025758) and financial contributions from Harvard University and its affiliated academic health care centers]. NR 62 TC 4 Z9 7 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2013 VL 98 IS 2 BP E206 EP E216 DI 10.1210/jc.2012-3294 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108DE UT WOS:000316270900002 PM 23341491 ER PT J AU Schult, TM Awosika, ER Schmunk, SK Hodgson, MJ Heymach, BL Parker, CD AF Schult, Tamara M. Awosika, Ebi R. Schmunk, Sandra K. Hodgson, Michael J. Heymach, Bria L. Parker, Celestine Dent TI Sitting on Stability Balls: Biomechanics Evaluation in a Workplace Setting SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE intervention effectiveness; office ergonomics; seating; stability ball ID LOW-BACK-PAIN; SEDENTARY TIME; EXERCISE BALL; OFFICE CHAIR; WORK; PERFORMANCE; DISCOMFORT; COMFORT; DISEASE; HEALTH AB Use of a stability ball alone and stability ball chair were evaluated in the Veterans Health Administration as possible alternatives to incorporate with regular office chair use. The evaluation of stability ball use was conducted under the auspices of a work site health promotion program as a cross-over trial with participants rotating through use of the stability ball, stability ball chair, and regular office chair on a monthly basis for a total duration of 3 months. Rotations on regular office chairs served as the control. Three medical facilities participated. A total of 193 employees completed a baseline questionnaire; 159 completed at least one post-rotation questionnaire. Self-reported measures included perceived posture when sitting, perceptions of overall balance, energy levels, job performance, safety, and pain. Use was associated with improvements in perceived posture (p < 0.0001) and energy levels (p = 0.007) for stability ball users compared with the office chair control, and improvements in perceived posture (p < 0.0001) and overall balance (p = 0.05) for stability ball chair users compared with the control. Use of stability balls at work decreases the likelihood of reporting pain from regular office chair use from approximately 45% to 21%. Alternatively, a high number of participants reported pain with use of the stability ball alone and stability ball chair, 42% and 45%, respectively. The perceived risks and benefits of stability ball use should be weighed when incorporating use. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplementary resource: Post-Active Sitting Device Questionnaire] C1 [Schult, Tamara M.; Awosika, Ebi R.; Schmunk, Sandra K.] Vet Hlth Adm, Off Publ Hlth, Minneapolis, MN 55417 USA. [Hodgson, Michael J.] Vet Hlth Adm, Off Publ Hlth, Washington, DC USA. [Heymach, Bria L.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Parker, Celestine Dent] Birmingham VA Med Ctr, Birmingham, AL USA. RP Schult, TM (reprint author), Vet Hlth Adm, Off Publ Hlth, 1 Vet Dr V68, Minneapolis, MN 55417 USA. EM tamara.schult@va.gov NR 25 TC 6 Z9 6 U1 4 U2 48 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD FEB 1 PY 2013 VL 10 IS 2 BP 55 EP 63 DI 10.1080/15459624.2012.748324 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 108XG UT WOS:000316329000004 PM 23252582 ER PT J AU Oxnard, GR Lo, PC Nishino, M Dahlberg, SE Lindeman, NI Butaney, M Jackman, DM Johnson, BE Janne, PA AF Oxnard, Geoffrey R. Lo, Peter C. Nishino, Mizuki Dahlberg, Suzanne E. Lindeman, Neal I. Butaney, Mohit Jackman, David M. Johnson, Bruce E. Jaenne, Pasi A. TI Natural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Epidermal growth factor receptor mutations; Exon 20 insertions ID GROWTH-FACTOR-RECEPTOR; MUTATIONS; INHIBITION; ADENOCARCINOMAS; GEFITINIB; GENE; BRAF; SENSITIVITY; MELANOMA; SURVIVAL AB Introduction: Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. Methods: NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. Results: One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. Conclusions: Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies. C1 [Oxnard, Geoffrey R.; Lo, Peter C.; Butaney, Mohit; Jackman, David M.; Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. [Oxnard, Geoffrey R.; Jackman, David M.; Johnson, Bruce E.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Nishino, Mizuki] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02114 USA. [Nishino, Mizuki] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02114 USA. [Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02114 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1234, Boston, MA 02114 USA. EM Geoffrey_Oxnard@DFCI.harvard.edu FU National Cancer Institute at the National Institutes of Health [R01-CA135257, P50-CA090578, K23-CA157631] FX This work was supported in part by the National Cancer Institute at the National Institutes of Health (R01-CA135257, P50-CA090578, K23-CA157631). G.R. Oxnard is a consultant/advisory board member for Genentech and Boehringer Ingelheim. D.M. Jackman is a consultant/advisory board member for Genentech and Foundation Medicine. B.E. Johnson is a consultant/advisory board member for Genentech, Pfizer, Chugai, Astra-Zeneca, Kew and Transgenomics. P.A. Janne is a consultant/advisory board member for Boehringer Ingelheim, Roche, Genentech, Abbot, Teva, Astra-Zeneca, Pfizer, and Sanofi. B.E. Johnson and P.A. Janne are coinventors on a patent held by the Dana-Farber Cancer Institute for the use of EGFR genotyping, and receive a share of post-market licensing revenue distributed by DFCI. Other authors have no potential conflicts of interest to disclose. NR 30 TC 39 Z9 39 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2013 VL 8 IS 2 BP 179 EP 184 DI 10.1097/JTO.0b013e3182779d18 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HA UT WOS:000316204900012 PM 23328547 ER PT J AU Malinoski, D Ewing, T Bhakta, A Schutz, R Imayanagita, B Casas, T Woo, N Margulies, D Barrios, C Lekawa, M Chung, R Bukur, M Kong, A AF Malinoski, Darren Ewing, Tyler Bhakta, Akash Schutz, Randi Imayanagita, Bryan Casas, Tamara Woo, Noah Margulies, Daniel Barrios, Cristobal Lekawa, Michael Chung, Rex Bukur, Marko Kong, Allen TI Which central venous catheters have the highest rate of catheter-associated deep venous thrombosis: A prospective analysis of 2,128 catheter days in the surgical intensive care unit SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Catheter-associated deep venous thrombosis; risk factors; central venous catheter; critical care ID UPPER-EXTREMITY; VEIN THROMBOSIS; NATURAL-HISTORY; TRAUMA PATIENTS; RISK-FACTORS; ANTICOAGULATION; COMPLICATIONS; TRIAL AB BACKGROUND: Catheter-associated deep venous thromboses (CADVTs) are a common occurrence in the surgical intensive care unit (SICU), necessitating central venous catheter (CVC) removal and replacement. Previous studies evaluating risk factors for CADVT in SICU patients are limited, and most lack a true denominator of all CVC days. We sought to determine the true incidence of and risk factors for CADVT based on patient characteristics as well as CVC site, type, and duration of insertion. METHODS: The following data from all SICU patients in two urban Level I trauma centerswere prospectively collected from 2009 to 2012: demographics, risk factors for DVT, CVC site/type/duration, and duplex results. Sites included the subclavian (SC), internal jugular (IJ), arm (for peripherally inserted central catheter [PICC] lines), and femoral. Types included multilumen (ML), introducer/hemodialysis (I/HD), and PICC. High-risk patients received weekly screening duplex examinations and a CADVT was defined as a DVT being detected on duplex with a CVC in place or within 7 days of removal. Rates of CADVT were normalized per 1,000 CVC days, and independent predictors of CADVT were determined using logistic regression. RESULTS: Data were complete for 184 patients, 354 CVCs, and 2,128 CVC days. Fifty-nine CADVTs were diagnosed in 28% of patients. Rates of CADVT were 9 per 1,000 catheter days for SC, 61 for IJ (p < 0.01 vs. SC), 27 for arm (p < 0.01), 36 for femoral (p < 0.01), 22 for ML, 57 for I/HD (p < 0.01 vs. ML), and 27 for PICC (p = 0.24). After adjusting for patient risk factors, predictors of CADVT included the IJ and arm sites (odds ratio, 6.0 and 3.0 compared with SC) and the I/HD type (odds ratio, 2.6 compared with ML, all p < 0.05). CONCLUSION: The IJ and arm sites and I/HD type are associated with increased CADVT. These data may be used to determine the optimal site and type of CVC for insertion. (J Trauma Acute Care Surg. 2013; 74: 454-462. Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Malinoski, Darren] Portland VA Med Ctr, Sect Surg Crit Care, Portland, OR USA. [Ewing, Tyler] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. [Schutz, Randi; Imayanagita, Bryan; Woo, Noah; Barrios, Cristobal; Lekawa, Michael; Kong, Allen] Univ Calif Irvine, Div Trauma & Crit Care, Irvine, CA USA. [Malinoski, Darren; Casas, Tamara; Chung, Rex; Bukur, Marko] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. [Bhakta, Akash] Midwestern Univ, Downers Grove, IL 60515 USA. RP Malinoski, D (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Sect Surg Crit Care, POB 1034 P3ANES, Portland, OR 97207 USA. EM malinosk@ohsu.edu NR 21 TC 7 Z9 8 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD FEB PY 2013 VL 74 IS 2 BP 454 EP 460 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 108UH UT WOS:000316321200029 PM 23354238 ER PT J AU van der Wilden, GM Schmidt, U Chang, YC Bittner, EA Cobb, JP Velmahos, GC Alam, HB de Moya, MA King, DR AF van der Wilden, Gwendolyn M. Schmidt, Ulrich Chang, Yuchiao Bittner, Edward A. Cobb, J. Perren Velmahos, George C. Alam, Hasan B. de Moya, Marc A. King, David R. TI Implementation of 24/7 intensivist presence in the SICU: Effect on processes of care SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Intensive care; 24/7; Leapfrog; intensivist; surgical intensive care unit ID CRITICALLY-ILL PATIENTS; HOSPITAL MORTALITY; UNIT; ADMISSION; ICU; SERVICES; RECOMMENDATIONS; ASSOCIATION; DELIVERY; WEEKENDS AB BACKGROUND: Staffing of attending intensivists 24 hours per day, 7 days per week (24/7) in the surgical intensive care unit (SICU) has unknown benefits. We hypothesized that 24/7 attending intensivist staffing in the SICU would improve outcomes and processes of care. METHODS: We retrospectively reviewed 26 months of admissions to our 20-bed SICU, comparing 13 months before and 13 months after addition of an in-house night intensivist to the existing day intensivist with a nighttime on-demand model. Primary outcomes were mortality, complications, SICU length of stay, and ventilator days. Secondary outcomes were use of intensivist-directed ancillary testing and therapies, as well as physician billing (relative value units per full-time equivalent [RVU/FTE]). RESULTS: A total of 2,829 patients were included: 1,408 before and 1,421 after 24/7 staffing. Baseline characteristics, mortality, complications, ventilation days, ICU and hospital length of stay, and readmission rate were similar between groups (all p > 0.05). Use of blood products and imaging tests (computed tomographic scans) were significantly reduced. Total RVU increased, as did the RVU/FTE ratio. CONCLUSION: Implementation of 24/7 staffing did not improve SICU morbidity or mortality but was associated with decreased blood product use and fewer axial imaging studies. The RVU/FTE ratio was improved. Overall health care value may be decreased under this model. (J Trauma Acute Care Surg. 2013;74: 563-567. Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [van der Wilden, Gwendolyn M.; Chang, Yuchiao; Velmahos, George C.; Alam, Hasan B.; de Moya, Marc A.; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. [Schmidt, Ulrich; Bittner, Edward A.; Cobb, J. Perren] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02141 USA. Harvard Univ, Sch Med, Boston, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 NR 25 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD FEB PY 2013 VL 74 IS 2 BP 563 EP 567 DI 10.1097/TA.0b013e31827880a8 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 108UH UT WOS:000316321200046 PM 23354251 ER PT J AU Katon, J Reiber, G Williams, MA Yanez, D Miller, E AF Katon, Jodie Reiber, Gayle Williams, Michelle A. Yanez, David Miller, Edith TI Weight Loss After Diagnosis with Gestational Diabetes and Birth Weight Among Overweight and Obese Women SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Gestational weight gain; Weight loss; Gestational diabetes; Birth weight; Obesity ID ANTEPARTUM MATERNAL METABOLISM; PREGNANCY OUTCOMES; GAIN; MELLITUS; RISK; ASSOCIATIONS; VALIDITY; TRENDS AB To determine if, among overweight or obese women with gestational diabetes (GDM), weight loss after GDM diagnosis is associated with lower infant birth weight within levels of overweight or obesity class. Overweight and obese women with singleton pregnancies managed for GDM at a large diabetes and pregnancy program located in Charlotte, NC between November 2000 and April 2010, were eligible for this retrospective cohort study. All were managed using a rigorous standardized clinical protocol. Clinical information including maternal pre-pregnancy body mass index, gestational weight gain, treatment, and medical and obstetric history was abstracted from medical records. The association of weight loss after GDM diagnosis and birth weight was analyzed using linear regression stratified by maternal pre-pregnancy overweight or obesity class (I, II/III). Of the 322 women in this study 19 % lost weight between diagnosis of GDM and delivery. After adjustment for maternal age, parity, race/ethnicity, gestational week at first hemoglobin A1c (A1C), A1C at diagnosis, weight gain prior to GDM, treatment with insulin or oral hypoglycemic agents, gestational age at delivery, and infant sex, weight loss was associated with 238.3 g lower mean infant birth weight among overweight women (95 % CI -393.72, -82.95 g), but was not associated with lower mean infant birth weight among obese class II/III women (95 % CI -275.61, 315.38 g). Weight loss, after diagnosis of GDM, is associated with lower infant birth weight among overweight women, but not among obese class II/III women. C1 [Katon, Jodie; Reiber, Gayle; Williams, Michelle A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Yanez, David] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Miller, Edith] Carolinas Med Ctr, Diabet & Pregnancy Program, Charlotte, NC 28203 USA. RP Katon, J (reprint author), Univ Washington, Sch Publ Hlth, Dept Epidemiol, POB 357236, Seattle, WA 98195 USA. EM jkaton@u.washington.edu FU NICHD NIH HHS [T32 HD052462] NR 29 TC 2 Z9 2 U1 2 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD FEB PY 2013 VL 17 IS 2 BP 374 EP 383 DI 10.1007/s10995-012-1044-5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 104PC UT WOS:000316005600021 PM 22692470 ER PT J AU Duce, JA Ayton, S Miller, AA Tsatsanis, A Lam, LQ Leone, L Corbin, JE Butzkueven, H Kilpatrick, TJ Rogers, JT Barnham, KJ Finkelstein, DI Bush, AI AF Duce, J. A. Ayton, S. Miller, A. A. Tsatsanis, A. Lam, L. Q. Leone, L. Corbin, J. E. Butzkueven, H. Kilpatrick, T. J. Rogers, J. T. Barnham, K. J. Finkelstein, D. I. Bush, A. I. TI Amine oxidase activity of beta-amyloid precursor protein modulates systemic and local catecholamine levels SO MOLECULAR PSYCHIATRY LA English DT Article DE beta-amyloid precursor protein; catecholamines; amine oxidation; neurotransmission ID CERULOPLASMIN-CATALYZED OXIDATION; ORTHO-DIANISIDINE DIHYDROCHLORIDE; INTERNATIONAL ENZYME UNITS; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; DOWN-SYNDROME; FERROXIDASE ACTIVITY; PICHIA-PASTORIS; GROWTH-HORMONE; ADIPOSE-TISSUE AB The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of beta-amyloid precursor protein (APP) is responsive to stress and is high in tissues rich in catecholamines. We recently reported that APP is a ferroxidase, subsuming, in neurons and other cells, the iron-export activity that ceruloplasmin mediates in glia. Here we report that, like ceruloplasmin, APP also oxidizes synthetic amines and catecholamines catalytically (K-m NE=0.27mM), through a site encompassing its ferroxidase motif and selectively inhibited by zinc. Accordingly, APP knockout mice have significantly higher levels of DA, NE and E in brain, plasma and select tissues. Consistent with this, these animals have increased resting heart rate and systolic blood pressure as well as suppressed prolactin and lymphocyte levels. These findings support a role for APP in extracellular catecholaminergic clearance. Molecular Psychiatry (2013) 18, 245-254; doi:10.1038/mp.2011.168; published online 3 January 2012 C1 [Duce, J. A.; Ayton, S.; Tsatsanis, A.; Lam, L. Q.; Barnham, K. J.; Finkelstein, D. I.; Bush, A. I.] Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Duce, J. A.; Ayton, S.; Butzkueven, H.; Kilpatrick, T. J.; Finkelstein, D. I.] Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia. [Miller, A. A.] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia. [Leone, L.; Barnham, K. J.; Bush, A. I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Corbin, J. E.] PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res & Cooperat Res C, Parkville, Vic, Australia. [Rogers, J. T.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Barnham, K. J.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Univ Melbourne, Mental Hlth Res Inst, 155 Oak St, Parkville, Vic 3052, Australia. EM abush@mhri.edu.au RI Bush, Ashley/A-1186-2007; Finkelstein, David/B-9617-2009 OI Bush, Ashley/0000-0001-8259-9069; Finkelstein, David/0000-0002-8167-4917 FU Australian Research Council; Australian National Health & Medical Research Council; Alzheimer's Association FX We thank Michael Cater for the generation of FD1(E415N)-APP695 and Keyla Perez for the generation of the FD1 peptide. This work was supported by funds from the Australian Research Council, the Australian National Health & Medical Research Council and the Alzheimer's Association. NR 69 TC 4 Z9 4 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2013 VL 18 IS 2 BP 245 EP 254 DI 10.1038/mp.2011.168 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 112BW UT WOS:000316567800017 PM 22212595 ER PT J AU Guha, M Castellanos-Rizaldos, E Liu, PF Mamon, H Makrigiorgos, GM AF Guha, Minakshi Castellanos-Rizaldos, Elena Liu, Pingfang Mamon, Harvey Makrigiorgos, G. Mike TI Differential strand separation at critical temperature: A minimally disruptive enrichment method for low-abundance unknown DNA mutations SO NUCLEIC ACIDS RESEARCH LA English DT Article ID METASTATIC COLORECTAL-CANCER; RAS GENE-MUTATIONS; COLD-PCR; KRAS MUTATIONS; ACQUIRED-RESISTANCE; SENSITIVE DETECTION; IDENTIFICATION; ADENOCARCINOMA; ALLELES; SAMPLES AB Detection of low-level DNA variations in the presence of wild-type DNA is important in several fields of medicine, including cancer, prenatal diagnosis and infectious diseases. PCR-based methods to enrich mutations during amplification have limited multiplexing capability, are mostly restricted to known mutations and are prone to polymerase or mis-priming errors. Here, we present Differential Strand Separation at Critical Temperature (DISSECT), a method that enriches unknown mutations of targeted DNA sequences purely based on thermal denaturation of DNA heteroduplexes without the need for enzymatic reactions. Target DNA is pre-amplified in a multiplex reaction and hybridized onto complementary probes immobilized on magnetic beads that correspond to wild-type DNA sequences. Presence of any mutation on the target DNA forms heteroduplexes that are subsequently denatured from the beads at a critical temperature and selectively separated from wild-type DNA. We demonstrate multiplexed enrichment by 100- to 400-fold for KRAS and TP53 mutations at multiple positions of the targeted sequence using two to four successive cycles of DISSECT. Cancer and plasma-circulating DNA samples containing traces of mutations undergo mutation enrichment allowing detection via Sanger sequencing or high-resolution melting. The simplicity, scalability and reliability of DISSECT make it a powerful method for mutation enrichment that integrates well with existing downstream detection methods. C1 [Guha, Minakshi; Castellanos-Rizaldos, Elena; Liu, Pingfang; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Mamon, Harvey; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mamon, Harvey; Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU NCI [R21 CA-111994, R21 CA-155615] FX NCI [R21 CA-111994 and R21 CA-155615, in part]. The contents of this article do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Funding for open access charge: Departmental funds. NR 28 TC 9 Z9 9 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2013 VL 41 IS 3 AR e50 DI 10.1093/nar/gks1250 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 109FM UT WOS:000316351800008 PM 23258702 ER PT J AU Metzger, O de Azambuja, E Bradbury, I Saini, KS Bines, J Simon, SD Van Dooren, V Aktan, G Pritchard, KI Wolff, AC Smith, I Jackisch, C Lang, I Untch, M Boyle, F Xu, BH Baselga, J Perez, EA Piccart-Gebhart, M AF Metzger-Filho, Otto de Azambuja, Evandro Bradbury, Ian Saini, Kamal S. Bines, Jose Simon, Sergio D. Van Dooren, Veerle Aktan, Gursel Pritchard, Kathleen I. Wolff, Antonio C. Smith, Ian Jackisch, Christian Lang, Istvan Untch, Michael Boyle, Frances Xu, Binghe Baselga, Jose Perez, Edith A. Piccart-Gebhart, Martine TI Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience SO ONCOLOGIST LA English DT Article DE Activation; Phase III clinical trials; Ethics committee/institutional review board AB Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries. Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. Results. South America had a significantly longer time to RA approval (median: 236 days, range: 21-257 days) than Europe (median: 52 days, range: 0-151 days), North America (median: 26 days, range: 22-30 days), and Asia-Pacific (median: 62 days, range: 37-75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21-257 days) than high-income (median: 47 days, range: 0-112 days) and lower-middle income economies (median: 57 days, range: 37-62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0-174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26-412 days). Conclusion. This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research. The Oncologist 2013; 18: 134-140 C1 [Metzger-Filho, Otto] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02215 USA. [Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Piccart-Gebhart, Martine] Univ Libre Brussels, Brussels, Belgium. [Metzger-Filho, Otto; de Azambuja, Evandro; Van Dooren, Veerle; Piccart-Gebhart, Martine] Breast European Adjuvant Study Team BrEAST Data C, Brussels, Belgium. [de Azambuja, Evandro; Piccart-Gebhart, Martine] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Saini, Kamal S.; Piccart-Gebhart, Martine] Breast Int Grp, Brussels, Belgium. [Bines, Jose; Simon, Sergio D.] Grp Brasileiro Estudos Canc Mama GBECAM Sao Paulo, Sao Paulo, Brazil. [Bines, Jose] INCA, Inst Nacl Canc, Rio De Janeiro, Brazil. [Simon, Sergio D.] Univ Fed Sao Paulo, Dept Oncol Clin, Sao Paulo, Brazil. [Aktan, Gursel] GlaxoSmithKline, Collegeville, PA USA. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Wolff, Antonio C.] Johns Hopkins Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Smith, Ian] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. [Smith, Ian] Inst Canc Res, London SW3 6JB, England. [Lang, Istvan] Natl Inst Oncol, Dept Med Oncol, Budapest, Hungary. [Untch, Michael] HELIOS Klin, Dept Gynecol & Obstet, Berlin, Germany. [Untch, Michael] HELIOS Klin, Multidisciplinary Breast Canc Ctr, Berlin, Germany. [Xu, Binghe] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA. [Baselga, Jose] SOLTI Breast Canc Res Grp, Barcelona, Spain. [Perez, Edith A.] Mayo Clin, Ctr Canc, Jacksonville, FL 32224 USA. RP Metzger, O (reprint author), Dana Farber Canc Inst, Div Womens Canc, 450 Brookline Ave,Yawkey Bldg 1238, Boston, MA 02215 USA. EM otto_metzger@dfci.harvard.edu OI Wolff, Antonio/0000-0003-3734-1063 FU GlaxoSmithKline FX The ALTTO trial is sponsored by GlaxoSmithKline. Collection, analysis, and interpretation of the current data were done independently by an academic group of statisticians (Frontier Science), I.B., and O.M.-F. NR 12 TC 5 Z9 5 U1 0 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD FEB PY 2013 VL 18 IS 2 BP 134 EP 140 DI 10.1634/theoncologist.2012-0342 PG 7 WC Oncology SC Oncology GA 102YJ UT WOS:000315880300003 PM 23359433 ER PT J AU Khanna, G Naranjo, A Hoffer, F Mullen, E Geller, J Gratias, EJ Ehrlich, PF Perlman, EJ Rosen, N Grundy, P Dome, JS AF Khanna, Geetika Naranjo, Arlene Hoffer, Fredric Mullen, Elizabeth Geller, James Gratias, Eric J. Ehrlich, Peter F. Perlman, Elizabeth J. Rosen, Nancy Grundy, Paul Dome, Jeffrey S. TI Detection of Preoperative Wilms Tumor Rupture with CT: A Report from the Children's Oncology Group SO RADIOLOGY LA English DT Article ID PERITONEAL CARCINOMATOSIS; INTEROBSERVER AGREEMENT; QUALITY ASSESSMENT; NEPHROBLASTOMA; CHILDHOOD; STUDY-5 AB Purpose: To retrospectively determine the diagnostic performance of computed tomography (CT) in identifying the presence or absence of preoperative Wilms tumor rupture. Materials and Methods: The cohort was derived from the AREN03B2 study of the Children's Oncology Group. The study was approved by the institutional review board and was compliant with HIPAA. Written informed consent was obtained before enrollment. The diagnosis of Wilms tumor rupture was established by central review of notes from surgery and/or pathologic examination. Seventy Wilms tumor cases with rupture were matched to 70 Wilms tumor controls without rupture according to age and tumor weight (within 6 months and 50 g, respectively). CT scans were independently reviewed by two radiologists, and the following CT findings were assessed: poorly circumscribed mass, perinephric fat stranding, peritumoral fat planes obscured, retroperitoneal fluid (subcapsular vs extracapsular), ascites beyond the cul-de-sac, peritoneal implants, ipsilateral pleural effusion, and intratumoral hemorrhage. All fluids were classified as hemorrhagic or nonhemorrhagic by using a cutoff of 30 HU. The relationship between CT findings and rupture was assessed with logistic regression models. Results: The sensitivity and specificity for detecting Wilms tumor rupture were 54% (36 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 1 and 70% (47 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 2. Interobserver agreement was substantial (kappa = 0.76). All imaging signs tested, except peritoneal implants, intratumoral hemorrhage, and subcapsular fluid, showed a significant association with rupture (P <= .02). The attenuation of ascitic fluid did not have a significant correlation with rupture (P = .9990). Ascites beyond the cul-de-sac was the single best indicator of rupture for both reviewers, followed by perinephric fat stranding and retroperitoneal fluid for reviewers 1 and 2, respectively (P < .01). Conclusion: CT has moderate specificity but relatively low sensitivity in the detection of preoperative Wilms tumor rupture. Ascites beyond the cul-de-sac, irrespective of attenuation, is most predictive of rupture. (C) RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120670/-/DC1 C1 [Khanna, Geetika] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Naranjo, Arlene] Univ Florida, Dept Biostat, Gainesville, FL USA. [Hoffer, Fredric; Rosen, Nancy] Qual Assurance Review Ctr, Providence, RI USA. [Mullen, Elizabeth] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mullen, Elizabeth] Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. [Geller, James] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Cincinnati, OH USA. [Gratias, Eric J.] Univ Tennessee, Coll Med, Childrens Hosp Erlanger, Div Hematol Oncol, Chattanooga, TN USA. [Ehrlich, Peter F.] Univ Michigan, CS Mott Childrens Hosp, Dept Surg, Ann Arbor, MI 48109 USA. [Perlman, Elizabeth J.] Childrens Mem Med Ctr, Dept Pathol, Chicago, IL USA. [Grundy, Paul] Stollery Childrens Hosp, Dept Pediat Hematol Oncol & Palliat Care, Edmonton, AB, Canada. [Dome, Jeffrey S.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. RP Khanna, G (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, 510 S Kingshighway Blvd,Campus Box 8131, St Louis, MO 63110 USA. EM khannag@mir.wustl.edu FU National Institutes of Health [U10 CA98543, U10 CA98413, CA29511] FX This research was supported by the National Institutes of Health (grants U10 CA98543, U10 CA98413, and CA29511). NR 19 TC 7 Z9 8 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2013 VL 266 IS 2 BP 610 EP 617 DI 10.1148/radiol.12120670 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 080DP UT WOS:000314221700027 PM 23192775 ER PT J AU Livi, CB Hardman, RL Christy, BA Dodds, SG Jones, D Williams, C Strong, R Bokov, A Javors, MA Ikeno, Y Hubbard, G Hasty, P Sharp, ZD AF Livi, Carolina B. Hardman, Rulon L. Christy, Barbara A. Dodds, Sherry G. Jones, Diane Williams, Charnae Strong, Randy Bokov, Alex Javors, Martin A. Ikeno, Yuji Hubbard, Gene Hasty, Paul Sharp, Zelton Dave TI Rapamycin extends life span of Rb1(+/-) mice by inhibiting neuroendocrine tumors SO AGING-US LA English DT Article DE mTOR; rapamycin; Rb1; neuroendocrine tumors ID GENETICALLY HETEROGENEOUS MICE; FATAL NEOPLASTIC DISEASES; RETINOBLASTOMA GENE; CALORIC RESTRICTION; DELAYED OCCURRENCE; GROWTH-HORMONE; CANCER; CARCINOGENESIS; RB; LONGEVITY AB Chronic treatment of mice with an enterically released formulation of rapamycin (eRapa) extends median and maximum life span, partly by attenuating cancer. The mechanistic basis of this response is not known. To gain a better understanding of these in vivo effects, we used a defined preclinical model of neuroendocrine cancer, Rb1(+/-) mice. Previous results showed that diet restriction (DR) had minimal or no effect on the lifespan of Rb1(+/-) mice, suggesting that the beneficial response to DR is dependent on pRb1. Since long-term eRapa treatment may at least partially mimic chronic DR in lifespan extension, we predicted that it would have a minimal effect in Rb1(+/-) mice. Beginning at 9 weeks of age until death, we fed Rb1(+/-) mice a diet without or with eRapa at 14 mg/kg food, which results in an approximate dose of 2.24 mg/kg body weight per day, and yielded rapamycin blood levels of about 4 ng/ml. Surprisingly, we found that eRapa dramatically extended life span of both female and male Rb1(+/-) mice, and slowed the appearance and growth of pituitary and decreased the incidence of thyroid tumors commonly observed in these mice. In this model, eRapa appears to act differently than DR, suggesting diverse mechanisms of action on survival and anti-tumor effects. In particular the beneficial effects of rapamycin did not depend on the dose of Rb1. C1 [Livi, Carolina B.; Christy, Barbara A.; Dodds, Sherry G.; Jones, Diane; Williams, Charnae; Hasty, Paul; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Livi, Carolina B.; Christy, Barbara A.; Dodds, Sherry G.; Jones, Diane; Williams, Charnae; Hasty, Paul; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, San Antonio, TX 78229 USA. [Hardman, Rulon L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Javors, Martin A.; Ikeno, Yuji; Hubbard, Gene] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Bokov, Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Livi, Carolina B.; Christy, Barbara A.; Strong, Randy; Javors, Martin A.; Ikeno, Yuji; Hubbard, Gene; Hasty, Paul; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Livi, Carolina B.; Christy, Barbara A.; Strong, Randy; Hasty, Paul; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Strong, Randy; Ikeno, Yuji] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Res Serv, San Antonio, TX 78229 USA. RP Sharp, ZD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. EM sharp@uthscsa.edu FU NIH [ISG 1RC2AG036613-01, 2P01AG017242-12, AG13319, UL1RR025767]; The Glenn Foundation for Medical Research; Department of Veteran Affairs (VA Merit Review Grant); Cancer Therapy Research Center [CA054174]; NCRR [UL 1RR025767]; RCMI [G12MD007591]; NIH (CTSA, Technology Transfer Resource); NIH (CBL) FX The authors gratefully acknowledge Gregory Friesenhahn for rapamycin blood level measurements, Jesse Usrey and Dr. Michael Duff Davis for technical assistance with MRI imaging. Viviane Diaz and the Nathan Shock Animal Core staff provided expert care for our mice. This work was supported by the following funding agencies: NIH (ISG 1RC2AG036613-01, Project 1, ZDS and PH; 2P01AG017242-12, PH; AG13319, YI; UL1RR025767, CTSA, Technology Transfer Resource to ZDS and CBL supported MRI imaging costs associated with this study), The Glenn Foundation for Medical Research (ZDS and YI), Department of Veteran Affairs (VA Merit Review Grant, YI). We would also like to thank the Cancer Therapy Research Center (CA054174), the NCRR (UL 1RR025767) and the RCMI (G12MD007591) for additional support. NR 42 TC 38 Z9 38 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD FEB PY 2013 VL 5 IS 2 BP 100 EP 110 PG 11 WC Cell Biology SC Cell Biology GA 104HL UT WOS:000315982700004 PM 23454836 ER PT J AU Brune, K Reng, F Ruff, CT Renner, B AF Brune, K. Reng, F. Ruff, C. T. Renner, B. TI Cardiovascular Risks of Cyclooxygenase Inhibitors (NSAIDs): Biomarkers for Risk Assessment? SO AKTUELLE RHEUMATOLOGIE LA German DT Article DE NSAID; natriuretic peptide; C-reactive peptide; cardiovascular risk; cyclooxygenase inhbitors ID BRAIN NATRIURETIC PEPTIDE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; C-REACTIVE PROTEIN; RHEUMATOID-ARTHRITIS; NT-PROBNP; COX-2 INHIBITORS; PAIN THERAPY; OLDER-ADULTS; PREDICT; MORTALITY AB Non-steroidal, anti-inflammatory drugs (NSAIDs, inhibitors of cyclooxygenases) are still worldwide the most intensively used remedies. These compounds are reliable therapeutics for muscle, joint, back, and traumatic pain. They cause, however, many unwanted side effects. Recently, the propensity of these compounds to cause cardiovascular diseases has been highlighted. As there are no alternatives available, attempts are made to single out those patients who are likely to develop unwanted cardiovascular drug effects when treated with NSAIDs. 2 widely used biomarkers were investigated as predictors of cardiovascular risks aggravated by the treatment with cyclooxygenase inhibitors. We here report on positive results of such evaluations employing the biomarker NTproBNP. C1 [Brune, K.; Renner, B.] Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, D-91054 Erlangen, Germany. [Reng, F.; Ruff, C. T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. RP Brune, K (reprint author), Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, D-91054 Erlangen, Germany. EM kay.brune@pharmakologie.uni-erlangen.de NR 27 TC 0 Z9 0 U1 6 U2 13 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0341-051X J9 AKTUEL RHEUMATOL JI Aktuelle Rheumatol. PD FEB PY 2013 VL 38 IS 1 BP 45 EP 49 DI 10.1055/s-0032-1301928 PG 5 WC Rheumatology SC Rheumatology GA 098EF UT WOS:000315528600006 ER PT J AU Blumenthal, DM Song, ZR Jena, AB Ferris, TG AF Blumenthal, Daniel M. Song, Zirui Jena, Anupam B. Ferris, Timothy G. TI Guidance for Structuring Team-Based Incentives in Healthcare SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OF-THE-LITERATURE; KAISER-PERMANENTE; ORGANIZATIONS; INNOVATION; LEADERSHIP; MORTALITY; PROSPECTS; MEDICARE; QUALITY; SAFETY AB New payment methods designed to incentivize more efficient care delivery are accelerating the movement of healthcare providers into organized provider groups. More efficient healthcare delivery requires explicit structuring of care delivery processes around teams of clinicians working toward common patient care goals. Provider organizations accepting new payment methods will need to design and implement compensation systems that provide incentives for team-based care. While lessons from studies performed both outside and inside healthcare provide some guidance on designing and implementing team-based incentives, organized delivery systems face several significant barriers to accomplishing this. (Am J Manag Care. 2013;19(2):e64-e70) C1 [Blumenthal, Daniel M.; Jena, Anupam B.; Ferris, Timothy G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Song, Zirui; Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Song, Zirui] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Blumenthal, DM (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Wang Ambulatory Care Ctr, 5th Fl,Ste 535,15 Parkman St, Boston, MA 02114 USA. EM dblumenthal1@partners.org FU NIA NIH HHS [F30 AG039175] NR 49 TC 7 Z9 7 U1 2 U2 12 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2013 VL 19 IS 2 BP E64 EP E70 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 099XI UT WOS:000315657600011 PM 23448116 ER PT J AU Romley, JA Jena, AB O'Leary, JF Goldman, DP AF Romley, John A. Jena, Anupam B. O'Leary, June F. Goldman, Dana P. TI Spending and Mortality in US Acute Care Hospitals SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID LIFE TREATMENT INTENSITY; REGIONAL-VARIATIONS; HEALTH; VARIABLES; OUTCOMES; QUALITY; ASSOCIATION; VALIDATION; SELECTION; SURVIVAL AB Background: Despite evidence that greater US Medicare spending is not associated with better quality of care at a regional level, recent studies suggest that greater hospital spending is associated with lower risk-adjusted mortality. Studies have been limited to older data, specific US states and conditions, and the Medicare population. Objectives: To analyze the association between hospital spending and risk-adjusted inpatient mortality for 6 major medical conditions in US acute care hospitals. Study Design: Retrospective cohort study of riskadjusted inpatient mortality, with hospital spending taken from the Dartmouth Atlas of Health Care. The study population included 2,635,510 patients admitted to 1201 US hospitals between 2003 and 2007. Methods: Patient-level logistic regression models were used to estimate the effect of hospital spending on inpatient mortality, controlling for mortality risk, comorbidities, community characteristics (eg, median household income in a patient's zip code), hospital volume and ownership, and admission year. Results: Patients treated at hospitals in the highest spending quintile (relative to the lowest) had lower risk-adjusted inpatient mortality for acute myocardial infarction (odds ratio [OR] 0.751, 95% confidence interval [CI] 0.656-0.859), congestive heart failure (OR 0.652, 95% CI 0.560-0.759), stroke (OR 0.852, 95% Cl, 0.739-0.983), and hip fracture (OR 0.691, 95% CI 0.545-0.876). Greater spending was associated with lower mortality primarily in nonteaching hospitals, hospitals with fewer than the median number of beds, and nonprofit/public hospitals. Conclusions: Greater hospital spending is associated with lower risk-adjusted inpatient mortality for major medical conditions in the United States. (Am J Manag Care. 2013;19(2):e46-e54) C1 [Romley, John A.; Goldman, Dana P.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Romley, John A.] RAND Corp, Santa Monica, CA USA. [Jena, Anupam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr, Boston, MA USA. [O'Leary, June F.] Pomona Coll, Dept Econ, Claremont, CA 91711 USA. RP Romley, JA (reprint author), RAND Corp, 3335 S Figueroa St,Unit A, Los Angeles, CA 90089 USA. EM romley@healthpolicy.usc.edu FU National Institute on Aging [1R03AG031990-A1]; Royal Center for Health Policy Simulation [P30AG024968] FX This research was supported by the National Institute on Aging (1R03AG031990-A1) and the Royal Center for Health Policy Simulation (P30AG024968). NR 41 TC 11 Z9 11 U1 1 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2013 VL 19 IS 2 BP E46 EP E54 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 099XI UT WOS:000315657600009 PM 23448114 ER PT J AU Fiedler, SE Dudiki, T Vijayaraghavan, S Carr, DW AF Fiedler, Sarah E. Dudiki, Tejasvi Vijayaraghavan, Srinivasan Carr, Daniel W. TI Loss of R2D2 Proteins ROPN1 and ROPN1L Causes Defects in Murine Sperm Motility, Phosphorylation, and Fibrous Sheath Integrity SO BIOLOGY OF REPRODUCTION LA English DT Article DE AKAP; fibrous sheath; OmniBank; PKA; ROPN1; sperm ID ZONA-PELLUCIDA BINDING; TYROSINE PHOSPHORYLATION; KINASE-A; EPIDIDYMAL MATURATION; REGULATORY SUBUNIT; MOUSE SPERMATOZOA; ANCHORING PROTEIN; MAMMALIAN SPERMATOZOA; ACROSOME REACTION; LATE STEPS AB The fibrous sheath (FS) is a flagellar cytoskeletal structure unique to sperm that surrounds the outer dense fibers and axoneme. Its primary components are A-kinase anchoring proteins (AKAPs) 3 and 4, which suggests that the FS affects flagellar beating via the scaffolding of signaling pathways necessary for motility. Sperm proteins ROPN1 and ROPN1L bind AKAP3. To determine the role of ROPN1 and ROPN1L in sperm function, we created mice deficient in ROPN1 (RKO), mice deficient in ROPN1L (RLKO), and double knockout mice (DKO). All three strains of mice had normal testicular morphology and spermatogenesis. Only the DKOs had obvious defects in sperm morphology (thinning and shredding of the principal piece), which was accompanied by a reduction in AKAP3 levels. RLKO mice had slightly reduced sperm motility and increased levels of ROPN1. RKO mice had moderately impaired motility and increased levels of ROPN1L. DKO sperm were immotile. We have previously determined that RKO male mice are subfertile, and DKO males are infertile. Together these data indicate that ROPN1L and ROPN1 compensate for each other in the absence of the opposing protein, possibly to maintain AKAP3 incorporation in the FS. Sperm from mice lacking ROPN1L exhibited reductions in both cAMP-dependent protein kinase (PKA) phosphorylation of a 270-kDa protein (perhaps FSCB), and in capacitation-induced tyrosine phosphorylation. Sperm from mice lacking ROPN1 had reduced levels of FSCB and increased tyrosine phosphorylation of noncapacitated sperm. These data demonstrate that mutations in ROPN1 and ROPN1L can cause defects in FS integrity, sperm motility, and PKA-dependent signaling processes, leading to male infertility. C1 [Fiedler, Sarah E.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR USA. [Fiedler, Sarah E.; Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Dudiki, Tejasvi; Vijayaraghavan, Srinivasan] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. RP Carr, DW (reprint author), Vet Affairs Med Ctr, Mail Code R&D8,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM carrd@ohsu.edu FU Department of Veterans' Affairs Biomedical Laboratory Research and Development Service; Eunice Kennedy Shriver National Institute of Child Health & Human Development [R03HD068668, HD38520] FX Supported by the Department of Veterans' Affairs Biomedical Laboratory Research and Development Service (D. W. C.) and by grants R03HD068668 and HD38520 to D. W. C. and S. V., respectively, from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health. NR 51 TC 16 Z9 16 U1 0 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 2013 VL 88 IS 2 AR 41 DI 10.1095/biolreprod.112.105262 PG 10 WC Reproductive Biology SC Reproductive Biology GA 103ZP UT WOS:000315958600001 PM 23303679 ER PT J AU Krishnan, MS Recht, A Bellon, JR Punglia, RS AF Krishnan, Monica S. Recht, Abram Bellon, Jennifer R. Punglia, Rinaa S. TI Trade-offs associated with axillary lymph node dissection with breast irradiation versus breast irradiation alone in patients with a positive sentinel node in relation to the risk of non-sentinel node involvement: implications of ACOSOG Z0011 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Decision analysis; Axillary lymph node dissection; Breast cancer ID RANDOMIZED CLINICAL-TRIAL; CANCER-PATIENTS; REGIONAL RECURRENCE; RADICAL MASTECTOMY; BIOPSY; WOMEN; CARCINOMA; RADIATION; METASTASES; MANAGEMENT AB Recent data suggest that axillary lymph node dissection (ALND) may be unnecessary for patients with positive sentinel lymph node biopsy (SLNB) receiving whole-breast irradiation (ACOSOG Z0011). The purpose of this study was to use decision analysis with simulated patients to determine subgroups with positive SLNB who may still benefit from ALND. We performed a decision analysis simulating axillary recurrence (ALR) risk, lymphedema, and quality of life following breast-conserving surgery (BCS) with positive SLNB and either completion ALND and whole-breast radiation (ALND + BRT) or breast radiation (BRT) alone. Simulated patients were divided into two risk groups based on the likelihood of disease in non-sentinel axillary nodes after positive SLNB: those with risk 30-60 % ("high-risk") and those with risk under 30 % ("low-risk," similar to average Z0011 patients). In simulated patients aged 55, BRT alone resulted in 1 month of additional QALE in the low-risk group versus ALND + BRT, while ALND + BRT resulted in 9.7 months of additional QALE in the high-risk group versus BRT alone. Overall survival was similar at 5 years in this simulation with either treatment in both groups, but ALND + BRT was superior to BRT alone at 20 years in the high-risk group (42 vs. 38 %). In the low-risk group, BRT alone is preferable unless ALR risk with BRT is greater than 1.6 % or lymphedema risk with ALND is under 10 %. Patients eligible for Z0011 but at a higher risk of residual nodal disease following BCS and positive SLNB may benefit from ALND + BRT, rather than BRT alone. C1 [Krishnan, Monica S.] Harvard Radiat Oncol Program, Boston, MA USA. [Recht, Abram] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Bellon, Jennifer R.; Punglia, Rinaa S.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Punglia, RS (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM rpunglia@lroc.harvard.edu NR 54 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2013 VL 138 IS 1 BP 205 EP 213 DI 10.1007/s10549-013-2418-0 PG 9 WC Oncology SC Oncology GA 099CX UT WOS:000315598200021 PM 23338762 ER PT J AU Carinci, AJ Pathak, R Young, M Christo, PJ AF Carinci, Adam J. Pathak, Ravi Young, Mark Christo, Paul J. TI Complementary and Alternative Treatments for Chronic Pelvic Pain SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Chronic pelvic pain; Complementary and alternative treatments; Pain ID POLLEN EXTRACT; DOUBLE-BLIND; WOMEN; ACUPUNCTURE; TRIAL AB Chronic pelvic pain (CPP) is a significant clinical entity that affects both men and women alike. The etiologies of CPP are multifactorial, and treatments are myriad. Complementary and Alternative Medicine (CAM) refers to non-allopathic health systems, and its use is popular in the United States. In particular, several recent studies have investigated the efficacy of various CAMpractices in the treatment of CPP. The authors systematically evaluated recent literature in this area by searching the PubMed database for English-language studies published between January 2007 and August 2012. C1 [Carinci, Adam J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pain Med,Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Pathak, Ravi; Young, Mark] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Christo, Paul J.] Johns Hopkins Univ, Sch Med, Div Pain Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. RP Carinci, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pain Med,Dept Anesthesia Crit Care & Pain Med, 15 Parkman St,Room 330, Boston, MA 02114 USA. EM acarinci@partners.org NR 25 TC 2 Z9 2 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD FEB PY 2013 VL 17 IS 2 AR 316 DI 10.1007/s11916-012-0316-5 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 099NT UT WOS:000315629200006 PM 23315022 ER PT J AU Kelkar, CA Desai, RS Kambadakone, A Shetty, SJ AF Kelkar, C. A. Desai, R. S. Kambadakone, A. Shetty, S. J. TI Multidetector CT and histological features of benign mesenchymoma of the infratemporal space: a rare case report SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE head and neck; infratemporal space; mesenchymoma ID TONGUE; NECK; HEAD AB Benign mesenchymoma is a soft tissue neoplasm composed of an admixture of two or more benign mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the infratemporal space in a 14-year-old boy is presented. In this case report we discuss the salient imaging and histopathological features of this rare entity. Dentomaxillofacial Radiology (2013) 42, 82002914. doi: 10.1259/dmfr/82002914 C1 [Desai, R. S.; Shetty, S. J.] Nair Hosp Dent Coll, Dept Oral & Maxillofacial Pathol, Bombay 400008, Maharashtra, India. [Kambadakone, A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shetty, SJ (reprint author), Nair Hosp Dent Coll, Dept Oral & Maxillofacial Pathol, Dr AL Nair Rd, Bombay 400008, Maharashtra, India. EM docsubu@yahoo.com NR 29 TC 0 Z9 1 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD FEB PY 2013 VL 42 IS 2 AR 82002914 DI 10.1259/dmfr/82002914 PG 7 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA 102FC UT WOS:000315829100013 PM 22282510 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI The camera as historian: amateur photographers and historical imagination, 18851918 SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jmifflin@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PD FEB 1 PY 2013 VL 11 IS 1 BP 91 EP 94 DI 10.1080/17460654.2012.757909 PG 4 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 098YK UT WOS:000315584800012 ER PT J AU Faustman, DL AF Faustman, Denise L. TI EBV infection and anti-CD3 treatment for Type 1 diabetes: bad cop, good cop? SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Editorial Material ID NF-KAPPA-B; T-CELLS; TNF; AUTOIMMUNITY; ANTIBODY; GENES C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Labs, MGH East, Boston, MA 02129 USA. [Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Labs, MGH East, Room 3602, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK057521] NR 17 TC 0 Z9 0 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD FEB PY 2013 VL 9 IS 2 BP 95 EP 97 DI 10.1586/ECI.12.101 PG 3 WC Immunology SC Immunology GA 098UP UT WOS:000315574900001 PM 23390937 ER PT J AU Lindenberger, E Lugassy, M Clark, E Bixby, K Sutcliffe, N Shah, R AF Lindenberger, Elizabeth Lugassy, Mara Clark, Elizabeth Bixby, Kathleen Sutcliffe, Natalie Shah, Ruchir TI Neurodegenerative Diseases: Palliative Care From Day One SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Lindenberger, Elizabeth] Mt Sinai Sch Med, New York, NY USA. [Lugassy, Mara] Metropolitan Jewish Hosp, New York, NY USA. [Clark, Elizabeth] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Bixby, Kathleen] Dept Vet Affairs, Washington, DC USA. [Sutcliffe, Natalie] James J Peters VA Med Ctr, Bronx, NY USA. [Shah, Ruchir] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 318 EP 319 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600018 ER PT J AU Talebreza, S Bernacki, R Kamal, A Swetz, K Tatum, P Stewart, T Widera, E Tucker, R AF Talebreza, Shaida Bernacki, Rachelle Kamal, Arif Swetz, Keith Tatum, Paul Stewart, Tanya Widera, Eric Tucker, Rodney TI Winning! Taking Your Presentation to the Next Level: From Abstract Submission to Magic at the Podium SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Talebreza, Shaida] Univ Utah, Sch Med, Salt Lake City, UT USA. [Bernacki, Rachelle] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kamal, Arif] Duke Univ, Durham, NC USA. [Swetz, Keith] Mayo Clin, Rochester, MN USA. [Tatum, Paul] Univ Missouri, Columbia, MO USA. [Stewart, Tanya] Evercare Oregon, Lake Oswego, OR USA. [Widera, Eric] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tucker, Rodney] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 321 EP 321 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600022 ER PT J AU Hultman, T Moment, A Cole, CA AF Hultman, Todd Moment, Amanda Cole, Corinne Alexander TI Conflict Resolution in the Workplace: Separated by a Common Language SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Hultman, Todd; Cole, Corinne Alexander] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moment, Amanda] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600027 ER PT J AU Periyakoil, V O'Neill, LB Bernacki, R Reilly, SS Thomas, JD Kapo, J Block, S Ferrell, B Weissman, D von Gunten, C AF Periyakoil, Vyjeyanthi O'Neill, Lynn Bunch Bernacki, Rachelle Reilly, Sandra Sanchez Thomas, Jane DeLima Kapo, Jennifer Block, Susan Ferrell, Betty Weissman, David von Gunten, Charles TI Mentoring Academy: An Immersive Learning Workshop for Interdisciplinary Professionals SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Periyakoil, Vyjeyanthi] Stanford Univ, Palo Alto, CA 94304 USA. [O'Neill, Lynn Bunch] Duke Univ, Durham, NC USA. [Bernacki, Rachelle; Thomas, Jane DeLima; Block, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reilly, Sandra Sanchez] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Thomas, Jane DeLima] Womens Hosp Med Ctr, Boston, MA USA. [Kapo, Jennifer] Yale Univ, Sch Med, New Haven, CT USA. [Ferrell, Betty] City Hope Natl Med Ctr, Duarte, CA USA. [Weissman, David] Palliat Care Educ LLC, Shorewood, WI USA. [von Gunten, Charles] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 324 EP 325 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600029 ER PT J AU Hultman, T Cox, S Paukstis, B Marshall, G AF Hultman, Todd Cox, Susan Paukstis, Beverly Marshall, Ginger TI Workforce Planning and Policy: Mind the Gap SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Hultman, Todd] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cox, Susan] Hosp & Palliat Care Greensboro, Greensboro, NC USA. [Paukstis, Beverly] Washington Home & Community Hosp, Washington, DC USA. [Marshall, Ginger] Carolina Palliat Care & Hosp Network, Charlotte, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 329 EP 329 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600037 ER PT J AU Bailey, A Leigh, A Redman, A Kennemer, D AF Bailey, Amos Leigh, Alexandra Redman, Amanda Kennemer, Darren TI Disease Update: More Deadly than AIDS, Dying of Hepatitis C Infection in the US SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Bailey, Amos; Kennemer, Darren] Birmingham VA Med Ctr, Birmingham, AL USA. [Leigh, Alexandra] Univ Alabama Birmingham, Birmingham Hosp, Birmingham VA Med Ctr, Birmingham, AL USA. [Redman, Amanda] Birmingham VA Med Ctr Birmingham, Birmingham, AL USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 333 EP 333 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600044 ER PT J AU Schell, J Arnold, R Weisbord, S Moss, A AF Schell, Jane Arnold, Robert Weisbord, Steven Moss, Alvin (Woody) TI The ABCs of Renal Palliative Care: Tools for Decision-Making and Symptom Management in Kidney Disease SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Schell, Jane] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Arnold, Robert] Univ Pittsburgh, Pittsburgh, PA USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Moss, Alvin (Woody)] W Virginia Univ, Sch Med, Morgantown, WV USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 339 EP 340 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600054 ER PT J AU McMichael, B Stewart, T Villars, P AF McMichael, Brian Stewart, Tanya Villars, Patrice TI "We Took a Sexual History, Now What Do We Do with the Answers?!" SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [McMichael, Brian] Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [Stewart, Tanya] Evercare Oregon, Lake Oswego, OR USA. [Villars, Patrice] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 341 EP 342 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600057 ER PT J AU Ullrich, C Liaw, SN Person, JL Warren, T Friebert, S AF Ullrich, Christina Liaw, Shih-Ning Person, Judi Lund Warren, Terri Friebert, Sarah TI The Concurrent Care Requirement for Children with Life-Threatening Illness: Challenges and Opportunities SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Ullrich, Christina] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. [Liaw, Shih-Ning] Univ Texas Houston, Sch Med, Houston, TX USA. [Person, Judi Lund] Natl Hosp & Palliat Care Org, Alexandria, VA USA. [Warren, Terri] Providence TrinityCare, Torrance, CA USA. [Friebert, Sarah] Akron Childrens Hosp, Akron, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 346 EP 346 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600064 ER PT J AU Bernacki, R Billings, JA Block, S AF Bernacki, Rachelle Billings, J. Andrew Block, Susan TI Timing and Selection of Patients for Advance Care Planning: Where is the Most Value Added? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Bernacki, Rachelle; Block, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 353 EP 354 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600076 ER PT J AU Aziz, W Getter, B Ross, J Sanchez-Reilly, S Lee, S AF Aziz, Wesam Getter, Benjamin Ross, Jeanette Sanchez-Reilly, Sandra Lee, Shuko TI YouTube as a Palliative Care Source of Information to "The World" SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Aziz, Wesam; Getter, Benjamin; Ross, Jeanette; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Aziz, Wesam; Getter, Benjamin; Ross, Jeanette; Sanchez-Reilly, Sandra; Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 360 EP 361 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600086 ER PT J AU Nash, R Bailey, A Bishop, J AF Nash, Ryan Bailey, Amos Bishop, Jeffrey TI A Palliative Response to the Anticipatory Corpse SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Nash, Ryan] Univ Alabama Birmingham, Ctr Palliat Care, Birmingham, AL USA. [Bailey, Amos] Birmingham VA Med Ctr, Birmingham, AL USA. [Bishop, Jeffrey] St Louis Univ, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 363 EP 364 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600091 ER PT J AU Bona, K Chabot, J Wolfe, J AF Bona, Kira Chabot, Joseph Wolfe, Joanne TI Meeting the Material Resource Needs of Families of Children With Cancer: Lessons for the Care of Children with Serious Illness SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Bona, Kira; Chabot, Joseph; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 366 EP 366 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600095 ER PT J AU Patel, C Abel, J Ross, J Lee, S Wiesenthal, A Sanchez-Reilly, S AF Patel, Chikal Abel, Jordan Ross, Jeanette Lee, Shuko Wiesenthal, Alison Sanchez-Reilly, Sandra TI Changing Practice by Changing Hearts: Medical Students Reflecting on Their Hands-on Palliative Care Experience SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Patel, Chikal; Abel, Jordan; Ross, Jeanette; Wiesenthal, Alison; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patel, Chikal; Abel, Jordan; Ross, Jeanette; Lee, Shuko; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 366 EP 367 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600096 ER PT J AU Kaiser, R Balish, M Bixby, K Tillman, D AF Kaiser, Robert Balish, Marshall Bixby, Kathleen Tillman, Douglas TI The Promise and Perils of BiPAP: Devising Effective Clinical Practice Guidelines for ALS Patients SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Kaiser, Robert] George Washington Univ, Sch Med, DC VA Med Ctr, Washington, DC 20052 USA. [Balish, Marshall; Tillman, Douglas] DC VA Med Ctr, Washington, DC USA. [Bixby, Kathleen] US Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 377 EP 378 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600113 ER PT J AU Waldman, E Tarquini, S AF Waldman, Elisha Tarquini, Sarah TI When Parents Want More: Negotiating Care in Pediatric Oncology With Palliative Chemotherapy SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Waldman, Elisha] Childrens Hosp, Boston, MA 02115 USA. [Waldman, Elisha; Tarquini, Sarah] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 379 EP 380 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600116 ER PT J AU Ahluwalia, S Luhrs, C Cortez, T Bailey, A Shreve, S Baum, H Zuccaro, M AF Ahluwalia, Sangeeta Luhrs, Carol Cortez, Therese Bailey, Amos Shreve, Scott Baum, Hannah Zuccaro, Mary TI The Use of Toolkits for Palliative Care Quality Improvement: The VA's "Strive for 65 Implementation Package'' SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Ahluwalia, Sangeeta; Baum, Hannah] Vet Adm, Los Angeles, CA USA. [Luhrs, Carol] VA New York Harbor Hlth Care Syst, Brooklyn, NY USA. [Cortez, Therese] VA Vet Integrated Serv Network 3, New York, NY USA. [Bailey, Amos] Birmingham VA Med Ctr, Birmingham, AL USA. [Shreve, Scott; Zuccaro, Mary] US Dept Vet Affairs, Lebanon, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 391 EP 391 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600133 ER PT J AU Worster, B Strand, J Lepp, A AF Worster, Brooke Strand, Jacob Lepp, Anya TI Palliative Care "Bucket List''-Skills Learned From Difficult Cases SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Worster, Brooke] Jefferson Univ Hosp, Philadelphia, PA USA. [Strand, Jacob] Mayo Clin, Rochester, MN USA. [Lepp, Anya] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 392 EP 393 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600135 ER PT J AU Wilson, E AF Wilson, Erica TI Dying Without a Home: Understanding and Responding to Palliative and End-of-Life Care Needs of Homeless Patients SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Wilson, Erica] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 403 EP 403 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600151 ER PT J AU Selvaggi, K Fitzgerald, K Moment, A Rickerson, E Bernacki, R AF Selvaggi, Kathy Fitzgerald, Katie Moment, Amanda Rickerson, Elizabeth Bernacki, Rachelle TI If It's Not One Thing, It's Another: The Pain Is Gone but the Suffering Continues SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Selvaggi, Kathy; Fitzgerald, Katie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moment, Amanda] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rickerson, Elizabeth] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bernacki, Rachelle] Dana Farber Canc Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 407 EP 407 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600157 ER PT J AU Bearden, D Patel, K Tucker, R Wozencraft, C Allman, R Ahmed, A AF Bearden, Donna Patel, Kanan Tucker, Rodney Wozencraft, Colin Allman, Richard Ahmed, Ali TI Six-Month Natural History of Hospitalized Medicare Beneficiaries With Heart Failure Referred for Hospice Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Bearden, Donna; Patel, Kanan; Wozencraft, Colin; Allman, Richard; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA. [Tucker, Rodney] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA. [Allman, Richard] Birmingham VA Med Ctr, Birmingham, AL USA. [Ahmed, Ali] VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 421 EP 422 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600179 ER PT J AU Ersek, M Smith, D Richardson, D Cannuscio, C Moore, D AF Ersek, Mary Smith, Dawn Richardson, Diane Cannuscio, Carolyn Moore, Denise TI A National Study Comparing End-of-life Care for Men and Women Veterans SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Ersek, Mary; Richardson, Diane; Moore, Denise] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Smith, Dawn] Univ Penn, Dept Vet Affairs, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 429 EP 430 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600191 ER PT J AU Jesus, OTV Qiu, A Carretero, E Oliver, DC Sanchez-Reilly, S AF Jesus, Ortiz Ter-Veen Qiu, Ann Carretero, Edgar Oliver, Dulce Cruz Sanchez-Reilly, Sandra TI Barriers to Quality End of Life Care for Latinos: Hospice Healthcare Professionals' Perspective SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Jesus, Ortiz Ter-Veen; Qiu, Ann; Carretero, Edgar; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Jesus, Ortiz Ter-Veen; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. [Oliver, Dulce Cruz] St Louis Univ, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 436 EP 437 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600202 ER PT J AU Riggs, J Woodby, L Burgio, K Bailey, FA Williams, B AF Riggs, Jennifer Woodby, Lesa Burgio, Kathryn Bailey, F. Amos Williams, Beverly TI Don't Get Weak in Your Compassion: Bereaved Next-of-Kin's Suggestions for Improving End-of-Life Care in VA Medical Centers SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Riggs, Jennifer] Birmingham Atlanta VA Geriatr Res Educ & Clin Cnt, Birmingham, AL USA. [Woodby, Lesa] Birmingham VA Med Ctr, Birmingham, AL USA. [Burgio, Kathryn; Williams, Beverly] Univ Alabama Birmingham, Birmingham, AL USA. [Bailey, F. Amos] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 450 EP 450 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600223 ER PT J AU Williams, B Bailey, FA Woodby, L Wittich, A Burgio, K AF Williams, Beverly Bailey, F. Amos Woodby, Lesa Wittich, Angelina Burgio, Kathryn TI We Thought We Had More Time: Exploring Next-of-Kin Accounts of Hospice and Palliative Care Discussions for Veterans Who Died in VA Medical Centers SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 13-16, 2013 CL New Orleans, LA SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc C1 [Williams, Beverly; Burgio, Kathryn] Univ Alabama Birmingham, Birmingham, AL USA. [Bailey, F. Amos] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. [Woodby, Lesa; Wittich, Angelina] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2013 VL 45 IS 2 BP 458 EP 459 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 100GE UT WOS:000315684600236 ER PT J AU Muh, SJ Streit, JJ Lenarz, CJ McCrum, C Wanner, JP Shishani, Y Moraga, C Nowinski, RJ Edwards, TB Warner, JJP Walch, G Gobezie, R AF Muh, Stephanie J. Streit, Jonathan J. Lenarz, Christopher J. McCrum, Christopher Wanner, John Paul Shishani, Yousef Moraga, Claudio Nowinski, Robert J. Edwards, T. Bradley Warner, Jon J. P. Walch, Gilles Gobezie, Reuben TI Resection arthroplasty for failed shoulder arthroplasty SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Resection arthroplasty; failed shoulder arthroplasty; reverse total shoulder; total shoulder arthroplasty; hemiarthroplasty; prosthesis resection; shoulder pain; shoulder replacement ID FRACTURES; INFECTION; HUMERUS; HEAD AB Background: As shoulder arthroplasty becomes more common, the number of failed arthroplasties requiring revision is expected to increase. When revision arthroplasty is not feasible, resection arthroplasty has been used in an attempt to restore function and relieve pain. Although outcomes data for resection arthroplasty exist, studies comparing the outcomes after the removal of different primary shoulder arthroplasties have been limited. Materials and methods: This was a retrospective multicenter reviewof 26 patients who underwent resection arthroplasty for failure of a primary arthroplasty at a mean follow-up of 41.8 months (range, 12-130 months). Resection arthroplasty was performed for 6 failed total shoulder arthroplasties (TSAs), 7 failed hemiarthroplasties, and 13 failed reverse TSAs. Results: Patients who underwent resection arthroplasty demonstrated significant improvement in visual analog scale pain score (6 +/- 4 preoperatively to 3 +/- 2 postoperatively). Mean active forward flexion and mean active external rotation decreased, but this difference was not significant. Subgroup analysis revealed that postoperative mean active forward flexion was significantly greater in patients undergoing resection arthroplasty after failed TSA than after reverse TSA (P = .01). Conclusions: Resection arthroplasty is effective in relieving pain, but patients have poor postoperative function. Patients with resection arthroplasty for failed reverse shoulder arthroplasty have worse function than those with failed hemiarthroplasty or TSA. Surgeons should be aware of this when assessing postoperative function. There is no difference in functional outcome between hemiarthroplasty and TSA. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Muh, Stephanie J.; Lenarz, Christopher J.; Wanner, John Paul; Shishani, Yousef] Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Case Shoulder & Elbow Serv, Cleveland, OH 44106 USA. [Streit, Jonathan J.] Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Orthopaed, Cleveland, OH 44106 USA. [McCrum, Christopher] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Moraga, Claudio] Clin Alemana Santiago, Dept Orthoped Surg, Santiago, Chile. [Nowinski, Robert J.] OrthoNeuro, New Albany, IN USA. [Edwards, T. Bradley] Fondren Orthoped Grp, Houston, TX USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. [Walch, Gilles] Shoulder Unit, Ctr Orthoped Santy, Lyon, France. [Gobezie, Reuben] Univ Hosp Cleveland, Cleveland Shoulder Inst, Cleveland, OH 44106 USA. RP Gobezie, R (reprint author), 5885 Landerbrook Dr,Suite 150, Mayfield Hts, OH 44124 USA. EM clevelandshoulder@gmail.com FU University Hospitals Case Medical Center Institutional Review Board (IRB) for Human Investigation [11-09-17] FX This study was approved by the University Hospitals Case Medical Center Institutional Review Board (IRB) for Human Investigation on Jan 5, 2010 (IRB grant number, 11-09-17), Joseph Gibbons, MD, Chairman. NR 26 TC 10 Z9 10 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD FEB PY 2013 VL 22 IS 2 BP 247 EP 252 DI 10.1016/j.jse.2012.05.025 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 100DG UT WOS:000315675400025 PM 22938790 ER PT J AU Jockel, CR Gardenal, RM Chen, NC Golden, RD Jupiter, JB Capomassi, M AF Jockel, Christopher R. Gardenal, R. Martin Chen, Neal C. Golden, Robert D. Jupiter, Jesse B. Capomassi, Miguel TI Intermediate-term outcomes for floating elbow and floating elbow variant injuries SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Floating elbow fracture; outcome ID ORTHOPEDIC TRAUMA; INTERNAL-FIXATION; DISLOCATED ELBOW; HUMERAL SHAFT; FRACTURES; FOREARM; MANAGEMENT; EXTREMITY AB Background: There are limited outcome studies describing floating elbow injuries. The purpose of this report is to describe patient outcomes after floating elbow injury using the American Shoulder and Elbow Surgeons (ASES) elbow assessment form. Materials and methods: From 1994 to 2004, 19 patients were retrospectively identified at 3 Level I trauma centers and returned for follow-up evaluation after treatment of their floating elbow injury. Patient outcomes were assessed based on physical examination and the ASES elbow form. Results: The 19 patients were evaluated at a mean of 6.7 years (range, 2.3-13.4 years) after treatment of their floating elbow injuries. The mean ASES elbow score was 89 (range, 13-99), and the mean visual analog scale satisfaction with elbow surgery was 8.7 (range, 7-10). Fifteen of 19 patients reported continued pain in the elbow. Patient age, arm dominance, type of humeral fixation, type of forearm fixation, open fracture, multiple surgeries, and fracture pattern were not significantly associated with outcomes. Nerve injury was associated with lower ASES elbow scores (P = .03). There was also a significant correlation between the ASES elbow score and follow-up time, indicating that patients with a longer duration of follow-up had better subjective outcomes (Spearman coefficient = 0.55; P = .02). Conclusion: Floating elbow fractures represent high-energy trauma and have significant associated injuries. Nerve injury is correlated with lower subjective outcomes. Patients continue to improve for several years with acceptable mid-term results. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Jockel, Christopher R.; Chen, Neal C.] Philadelphia Hand Ctr, Philadelphia, PA 19107 USA. [Gardenal, R. Martin; Capomassi, Miguel] Inst Jaime Slullitel, Rosario, Argentina. [Gardenal, R. Martin; Capomassi, Miguel] Hosp Emergencias HECA, Rosario, Argentina. [Golden, Robert D.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golden, Robert D.; Jupiter, Jesse B.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Jockel, CR (reprint author), Philadelphia Hand Ctr, 834 Chestnut St,Ste G114, Philadelphia, PA 19107 USA. EM cjockel79@gmail.com OI Gardenal, Ricardo Martin/0000-0003-0013-9275 FU Orthopaedic Trauma Association (OTA) [6]; AO Foundation; publisher Elsevier Thieme FX This research was supported by the Orthopaedic Trauma Association (OTA) research grant #6.; Neal C. Chen, MD, is an unpaid consultant for Medartis. Jesse B. Jupiter, MD, is a paid consultant for OHK Medical Devices Inc and an unpaid consultant for Synthes, Eisomed. He receives research support from the AO Foundation, and receives royalties from the publisher Elsevier Thieme. The other authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article. NR 23 TC 3 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD FEB PY 2013 VL 22 IS 2 BP 280 EP 285 DI 10.1016/j.jse.2012.11.008 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 100DG UT WOS:000315675400030 PM 23352472 ER PT J AU Miller, MW Reardon, AF Wolf, EJ Prince, LB Hein, CL AF Miller, Mark W. Reardon, Annemarie F. Wolf, Erika J. Prince, Lauren B. Hein, Christina L. TI Alcohol and Drug Abuse Among US Veterans: Comparing Associations With Intimate Partner Substance Abuse and Veteran Psychopathology SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VA HEALTH-CARE; RELATIONSHIP STABILITY; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; COMMUNITY SAMPLE; HEAVY DRINKING; PTSD; COMORBIDITY; DEPENDENCE AB This study examined the relative influences of posttraumatic stress disorder (PTSD), other psychopathology, and intimate partner alcohol and drug use on substance-related problems in U.S. veterans (242 couples, N = 484). Hierarchical regression analyses revealed that partner alcohol and drug use severity explained more variance in veteran alcohol use and drug use (20% and 13%, respectively) than did veteran PTSD, adult antisocial behavior, or depression symptoms combined (6% for veteran alcohol use; 7% for veteran drug use). Findings shed new light on the influence of relationship factors on veteran alcohol and drug use and underscore the importance of couples-oriented approaches to treating veterans with comorbid PTSD and substance abuse. C1 [Miller, Mark W.; Wolf, Erika J.; Prince, Lauren B.; Hein, Christina L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.; Wolf, Erika J.; Prince, Lauren B.; Hein, Christina L.] Dept Psychiat, Boston, MA USA. [Miller, Mark W.; Wolf, Erika J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reardon, Annemarie F.] VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU CSRD VA [I01 CX000431]; NIMH NIH HHS [R01 MH079806, R01MH079806] NR 39 TC 2 Z9 2 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2013 VL 26 IS 1 BP 71 EP 76 DI 10.1002/jts.21773 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 092CH UT WOS:000315095900009 PM 23325433 ER PT J AU Iverson, KM Litwack, SD Pineles, SL Suvak, MK Vaughn, RA Resick, PA AF Iverson, Katherine M. Litwack, Scott D. Pineles, Suzanne L. Suvak, Michael K. Vaughn, Rachel A. Resick, Patricia A. TI Predictors of Intimate Partner Violence Revictimization: The Relative Impact of Distinct PTSD Symptoms, Dissociation, and Coping Strategies SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; WOMEN; SELF; REABUSE; TRAUMA; SCALE; RESOURCES; SURVIVORS; MEDIATOR AB Psychological distress and coping strategies following intimate partner violence (IPV) victimization may impact survivors' risk for future IPV. The current study prospectively examined the impact of distinct posttraumatic stress disorder (PTSD) symptom clusters (reexperiencing, avoidance, numbing, and hyperarousal), dissociation, and coping strategies (engagement and disengagement coping) on IPV revictimization among recently abused women. Women (N = 69) who were seeking services for IPV and experienced their most recent episode of physical IPV between 2 weeks and 6 months prior to study enrollment completed measures of physical IPV, psychological distress, and coping strategies at baseline and at 6-month follow-up. The women averaged 36 years of age and 67% of the sample was African American. Separate Poisson regression analyses revealed that PTSD hyperarousal symptoms, dissociation, engagement coping, and disengagement coping each significantly predicted physical IPV revictimization at the 6-month follow-up (with effect sizes ranging from a 1.20-1.34 increase in the likelihood of Time 2 physical IPV with a 1 SD increase in the predictor). When these significant predictors were examined together in a single Poisson regression model, only engagement and disengagement coping were found to predict physical IPV revictimization such that disengagement coping was associated with higher revictimization risk (1.29 increase in the likelihood of Time 2 physical IPV with one SD increase in disengagement coping) and engagement coping was associated with lower revictimization risk (1.30 decrease in the likelihood of Time 2 physical IPV with one SD increase in engagement coping). The current findings suggest that coping strategies are important and potentially malleable predictors of physical IPV revictimization. C1 [Iverson, Katherine M.; Pineles, Suzanne L.; Suvak, Michael K.; Vaughn, Rachel A.; Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Iverson, Katherine M.; Pineles, Suzanne L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Litwack, Scott D.] VA Boston Healthcare Syst, Behav Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov FU NIMH NIH HHS [1-R01-MH55542] NR 52 TC 17 Z9 18 U1 5 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2013 VL 26 IS 1 BP 102 EP 110 DI 10.1002/jts.21781 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 092CH UT WOS:000315095900013 PM 23417878 ER PT J AU Jakupcak, M Hoerster, KD Blais, RK Malte, CA Hunt, S Seal, K AF Jakupcak, Matthew Hoerster, Katherine D. Blais, Rebecca K. Malte, Carol A. Hunt, Stephen Seal, Karen TI Readiness for Change Predicts VA Mental Healthcare Utilization Among Iraq and Afghanistan War Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRANSTHEORETICAL MODEL; RISK-FACTORS; DIAGNOSES; PTSD; PSYCHOTHERAPY; ASSOCIATION; ENGAGEMENT; SERVICES; COMBAT AB Many veterans present to Veteran Affairs (VA) care intending to seek mental health treatment for symptoms of posttraumatic stress disorder (PTSD), depression, and/or alcohol misuse, yet most subsequently underutilize mental health care. This study examined the association of readiness for change with outpatient VA mental health care utilization in 104 treatment-seeking Iraq and Afghanistan war veterans who screened positive for PTSD, depression, and/or alcohol misuse at intake. Multivariate analyses demonstrated that readiness for change assessed at intake was positively associated (Incident Rate Ratio [IRR] = 1.22) with prospective outpatient mental health care utilization with demographic factors, military characteristics, and mental health burden in the model. Results suggest that interventions that target readiness to change, such as motivational interviewing, may improve treatment utilization in veterans presenting for mental health care. C1 [Jakupcak, Matthew; Hoerster, Katherine D.; Blais, Rebecca K.; Malte, Carol A.; Hunt, Stephen] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Jakupcak, Matthew; Hoerster, Katherine D.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Blais, Rebecca K.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA USA. [Seal, Karen] Univ Calif San Francisco, Dept Med & Psychiat, San Francisco, CA 94143 USA. RP Jakupcak, M (reprint author), VA Puget Sound Hlth Care Syst, Deployment Hlth Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM matthew.jakupcak@va.gov NR 22 TC 4 Z9 4 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2013 VL 26 IS 1 BP 165 EP 168 DI 10.1002/jts.21768 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 092CH UT WOS:000315095900021 PM 23319359 ER PT J AU Fontana, CR Lerman, MA Patel, N Grecco, C Costa, CAD Amiji, MM Bagnato, VS Soukos, NS AF Fontana, Carla R. Lerman, Mark A. Patel, Niraj Grecco, Clovis de Souza Costa, Carlos A. Amiji, Mansoor M. Bagnato, Vanderlei S. Soukos, Nikolaos S. TI Safety assessment of oral photodynamic therapy in rats SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Photodynamic therapy; Photosensitizers; Histological analysis; Fluorescence ID STAPHYLOCOCCUS-AUREUS; WOUND INFECTIONS; CANDIDA-ALBICANS; METHYLENE-BLUE; IN-VITRO; NANOPARTICLES; INACTIVATION; LIGHT; PHOTOSENSITIZERS; PHOTOFRIN AB Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (PhotogemA (R)), PhotodithazineA (R), methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with PhotogemA (R), PhotodithazineA (R), MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue. C1 [Fontana, Carla R.] Univ Sao Paulo State UNESP, Sch Pharmaceut Sci, Dept Clin Anal, BR-14801960 Araraquara, Sau Paulo, Brazil. [Lerman, Mark A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Patel, Niraj; Soukos, Nikolaos S.] Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. [Grecco, Clovis; Bagnato, Vanderlei S.] Univ Sao Paulo, Inst Phys Sao Carlos, BR-15980900 Sao Carlos, Sau Paulo, Brazil. [de Souza Costa, Carlos A.] Univ Sao Paulo State UNESP, Dent Sch Araraquara, BR-14801960 Araraquara, Sau Paulo, Brazil. [Patel, Niraj; Amiji, Mansoor M.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Fontana, CR (reprint author), Univ Sao Paulo State UNESP, Sch Pharmaceut Sci, Dept Clin Anal, 1621 Expedicionarios Brasil St, BR-14801960 Araraquara, Sau Paulo, Brazil. EM fontanacr@fcfar.unesp.br RI Amiji, Mansoor/A-4365-2014; Grecco, Clovis/L-2401-2014; USP, CePOF/J-3608-2015; de Souza Costa, Carlos Alberto/C-6799-2012; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; Bagnato, Vanderlei/C-3133-2012 OI Amiji, Mansoor/0000-0001-6170-881X; de Souza Costa, Carlos Alberto/0000-0002-7455-6867; FU FAPESP FX This work was supported by FAPESP. NR 38 TC 7 Z9 7 U1 0 U2 19 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 J9 LASER MED SCI JI Lasers Med. Sci. PD FEB PY 2013 VL 28 IS 2 BP 479 EP 486 DI 10.1007/s10103-012-1091-6 PG 8 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA 098WI UT WOS:000315579400018 PM 22467011 ER PT J AU Priyadarshini, R Cugini, C Arndt, A Chen, T Tjokro, NO Goodman, SD Davey, ME AF Priyadarshini, Richa Cugini, Carla Arndt, Annette Chen, Tsute Tjokro, Natalia O. Goodman, Steven D. Davey, Mary E. TI The nucleoid-associated protein HU beta affects global gene expression in Porphyromonas gingivalis SO MICROBIOLOGY-SGM LA English DT Article ID INTEGRATION HOST FACTOR; DNA-BINDING PROTEIN; ESCHERICHIA-COLI; HEME UTILIZATION; INCREASED SENSITIVITY; PERIODONTAL-DISEASE; BACILLUS-SUBTILIS; SOS INDUCTION; CRUCIFORM DNA; CELL-DIVISION AB HU is a non-sequence-specific DNA-binding protein and one of the most abundant nucleoid-associated proteins in the bacterial cell. Like Escherichia coli, the genome of Porphyromonas gingivalis is predicted to encode both the HU alpha (PG1258) and the HU beta (PG0121) subunit. We have previously reported that PG0121 encodes a non-specific DNA-binding protein and that PG0121 is co-transcribed with the K-antigen capsule synthesis operon. We also reported that deletion of PG0121 resulted in downregulation of capsule operon expression and produced a P. gingivalis strain that is phenotypically deficient in surface polysaccharide production. Here, we show through complementation experiments in an E. coli MG1655 hupAB double mutant strain that PG0121 encodes a functional HU homologue. Microarray and quantitative RT-PCR analysis were used to further investigate global transcriptional regulation by HU beta using comparative expression profiling of the PG0121 (HU beta) mutant strain to the parent strain, W83. Our analysis determined that expression of genes encoding proteins involved in a variety of biological functions, including iron acquisition, cell division and translation, as well as a number of predicted nucleoid associated proteins were altered in the PG0121 mutant. Phenotypic and quantitative real-time-PCR (qRT-PCR) analyses determined that under iron-limiting growth conditions, cell division and viability were defective in the PG0121 mutant. Collectively, our studies show that PG0121 does indeed encode a functional HU homologue, and HU beta has global regulatory functions in P. gingivalis; it affects not only production of capsular polysaccharides but also expression of genes involved in basic functions, such as cell wall synthesis, cell division and iron uptake. C1 [Priyadarshini, Richa; Cugini, Carla; Chen, Tsute; Davey, Mary E.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Priyadarshini, Richa; Cugini, Carla; Chen, Tsute; Davey, Mary E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Arndt, Annette] Univ Ulm, Inst Microbiol & Biotechnol, D-89069 Ulm, Germany. [Tjokro, Natalia O.; Goodman, Steven D.] Univ So Calif, Div Biomed Sci, Herman Ostrow Sch Dent, Los Angeles, CA USA. RP Davey, ME (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. EM mdavey@forsyth.org FU National Institute of Dental and Craniofacial Research NIDCR [DE-019117] FX The authors wish to thank Jennifer Downey for her technical expertise and advice. This work was supported by a grant from the National Institute of Dental and Craniofacial Research NIDCR (DE-019117) to M. E. D. NR 75 TC 7 Z9 7 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD FEB PY 2013 VL 159 BP 219 EP 229 DI 10.1099/mic.0.061002-0 PN 2 PG 11 WC Microbiology SC Microbiology GA 103QL UT WOS:000315933900002 PM 23175503 ER PT J AU Cugini, C Stephens, DN Nguyen, D Kantarci, A Davey, ME AF Cugini, Carla Stephens, Danielle N. Daniel Nguyen Kantarci, Alpdogan Davey, Mary E. TI Arginine deiminase inhibits Porphyromonas gingivalis surface attachment SO MICROBIOLOGY-SGM LA English DT Article ID PSEUDOMONAS-AERUGINOSA; PERIODONTAL-DISEASE; ESCHERICHIA-COLI; ORAL BACTERIA; PEPTIDYLARGININE DEIMINASE; BACTEROIDES-GINGIVALIS; CATALYTIC MECHANISM; CRYSTAL-STRUCTURES; CARIES EXPERIENCE; BIOFILM FORMATION AB The oral cavity is host to a complex microbial community whose maintenance depends on an array of cell-to-cell interactions and communication networks, with little known regarding the nature of the signals or mechanisms by which they are sensed and transmitted. Determining the signals that control attachment, biofilm development and outgrowth of oral pathogens is fundamental to understanding pathogenic biofilm development. We have previously identified a secreted arginine deiminase (ADI) produced by Streptococcus intermedius that inhibited biofilm development of the commensal pathogen Porphyromonas gingivalis through downregulation of genes encoding the major (fimA) and minor (mfa1) fimbriae, both of which are required for proper biofilm development. Here we report that this inhibitory effect is dependent on enzymic activity. We have successfully cloned, expressed and defined the conditions to ensure that ADI from S. intermedius is enzymically active. Along with the cloning of the wild-type allele, we have created a catalytic mutant (ADIC399S), in which the resulting protein is not able to catalyse the hydrolysis of L-arginine to L-citrulline. P. gingivalis is insensitive to the ADIC399S catalytic mutant, demonstrating that enzymic activity is required for the effects of ADI on biofilm formation. Biofilm formation is absent under L-arginine-deplete conditions, and can be recovered by the addition of the amino acid. Taken together, the results indicate that arginine is an important signal that directs biofilm formation by this anaerobe. Based on our findings, we postulate that ADI functions to reduce arginine levels and, by a yet to be identified mechanism, signals P. gingivalis to alter biofilm development. ADI release from the streptococcal cell and its cross-genera effects are important findings in understanding the nature of inter-bacterial signalling and biofilm-mediated diseases of the oral cavity. C1 [Cugini, Carla; Davey, Mary E.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Cugini, Carla; Davey, Mary E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stephens, Danielle N.; Daniel Nguyen; Kantarci, Alpdogan] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. RP Davey, ME (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. EM mdavey@forsyth.org FU National Institutes of Health-National Institute of Dental and Craniofacial Research [DE022484 NIH-NIDCR, DE019117 NIH-NIDCR, DE20906 NIH-NIDCR] FX This work was supported by National Institutes of Health-National Institute of Dental and Craniofacial Research grants DE022484 NIH-NIDCR, awarded to C. C., DE019117 NIH-NIDCR, awarded to M. E. D, and DE20906 NIH-NIDCR, awarded to A. K. NR 54 TC 7 Z9 7 U1 1 U2 13 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD FEB PY 2013 VL 159 BP 275 EP 285 DI 10.1099/mic.0.062695-0 PN 2 PG 11 WC Microbiology SC Microbiology GA 103QL UT WOS:000315933900008 PM 23242802 ER PT J AU Molineros, JE Maiti, AK Sun, C Looger, LL Han, SZ Kim-Howard, X Glenn, S Adler, A Kelly, JA Niewold, TB Gilkeson, GS Brown, EE Alarcon, GS Edberg, JC Petri, M Ramsey-Goldman, R Reveille, JD Vila, LM Freedman, BI Tsao, BP Criswell, LA Jacob, CO Moore, JH Vyse, TJ Langefeld, CL Guthridge, JM Gaffney, PM Moser, KL Scofield, RH Alarcon-Riquelme, ME Williams, SM Merrill, JT James, JA Kaufman, KM Kimberly, RP Harley, JB Nath, SK AF Molineros, Julio E. Maiti, Amit K. Sun, Celi Looger, Loren L. Han, Shizhong Kim-Howard, Xana Glenn, Stuart Adler, Adam Kelly, Jennifer A. Niewold, Timothy B. Gilkeson, Gary S. Brown, Elizabeth E. Alarcon, Graciela S. Edberg, Jeffrey C. Petri, Michelle Ramsey-Goldman, Rosalind Reveille, John D. Vila, Luis M. Freedman, Barry I. Tsao, Betty P. Criswell, Lindsey A. Jacob, Chaim O. Moore, Jason H. Vyse, Timothy J. Langefeld, Carl L. Guthridge, Joel M. Gaffney, Patrick M. Moser, Kathy L. Scofield, R. Hal Alarcon-Riquelme, Marta E. Williams, Scott M. Merrill, Joan T. James, Judith A. Kaufman, Kenneth M. Kimberly, Robert P. Harley, John B. Nath, Swapan K. CA BIOLUPUS Network TI Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production SO PLOS GENETICS LA English DT Article ID CLASS-SWITCH RECOMBINATION; WHOLE-GENOME ASSOCIATION; BINDING-PROTEIN; RIG-I; POPULATION-STRUCTURE; AFRICAN-AMERICANS; REVISED CRITERIA; GENE DISCOVERY; DISEASE GENES; GENOTYPE DATA AB Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD = 6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio similar to 1.5). Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P-meta = 5.20x10(-14); odds ratio, 95% confidence interval = 0.82 (0.78-0.87)], and two missense variants, rs1990760 (Ala946Thr) [P-meta = 3.08x10(-7); 0.88 (0.84-0.93)] and rs10930046 (Arg460His) [P-dom = 1.16x10(-8); 0.70 (0.62-0.79)]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis. C1 [Molineros, Julio E.; Maiti, Amit K.; Sun, Celi; Han, Shizhong; Kim-Howard, Xana; Glenn, Stuart; Adler, Adam; Kelly, Jennifer A.; Guthridge, Joel M.; Gaffney, Patrick M.; Moser, Kathy L.; Scofield, R. Hal; Alarcon-Riquelme, Marta E.; James, Judith A.; Kaufman, Kenneth M.; Nath, Swapan K.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA USA. [Han, Shizhong] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Niewold, Timothy B.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Niewold, Timothy B.] Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. [Brown, Elizabeth E.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Kimberly, Robert P.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Div Rheumatol, Feinberg Sch Med, Chicago, IL 60611 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Dept Rheumatol & Clin Immunogenet, Houston, TX USA. [Vila, Luis M.] Univ Puerto Rico, Div Rheumatol, Dept Med, San Juan, PR 00936 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Tsao, Betty P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA. [Jacob, Chaim O.] Univ So Calif, Dept Med, Los Angeles, CA USA. [Moore, Jason H.] Dartmouth Med Sch, Dept Genet, Lebanon, NH USA. [Vyse, Timothy J.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England. [Langefeld, Carl L.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Wake Forest, NC USA. [Moser, Kathy L.; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA. [Alarcon-Riquelme, Marta E.] Univ Granada, Ctr Genom & Invest Oncol GENyO Pfizer, Granada, Spain. [Williams, Scott M.] Dartmouth Coll, Dept Genet, Geisel Sch Med, Hanover, NH 03755 USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Res Program, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Molineros, JE (reprint author), Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Swapan-Nath@omrf.org OI Kimberly, Robert/0000-0002-5330-3086; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660 FU National Institutes of Health [AR060366, AR049084, AI094377, AR053483, AR33062, RR020143, RR0155577, AI082714, AR058554, AI083194, AI024717, GM103510, AR057172]; U.S. Department of Defense [AI082714, AI024717, PR094002, AR002138, AR30692, RR025741, AR042460, AI031584, AI101934, AR062277, AR048940, AR043814, DE018209, AI062629, DE015223, RR027190, P60 AR053308, R01 AR44804, M01 RR-00079, UL1 TR000165]; U.S. Department of Veterans Affairs [IMMA 9]; Alliance for Lupus Research; Swedish Research Council; Kirkland Scholar Award; Instituto de Salud Carlos III (European Union Fonds Europeen de Developpement Regional (FEDER)) [PS09/00129]; European Science Foundation (BIOLUPUS) FX This work was supported by grants from the National Institutes of Health (AR060366, AR049084, AI094377, AR053483, AR33062, RR020143, RR0155577, AI082714, AR058554, AI083194, AI024717, GM103510, AR057172), the U.S. Department of Defense (PR094002, AR002138, AR30692, RR025741, AR042460, AI024717, AI031584, AI101934, AR062277, AR048940, AR043814, DE018209, AI082714, AI062629, DE015223, RR027190, PR094002, P60 AR053308, R01 AR44804, M01 RR-00079, UL1 TR000165), the U.S. Department of Veterans Affairs (IMMA 9), the Alliance for Lupus Research, the Swedish Research Council, Kirkland Scholar Award, Instituto de Salud Carlos III (PS09/00129, co-financed through the European Union Fonds Europeen de Developpement Regional (FEDER)), and European Science Foundation (BIOLUPUS). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 37 Z9 38 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD FEB PY 2013 VL 9 IS 2 AR e1003222 DI 10.1371/journal.pgen.1003222 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 099RG UT WOS:000315638300005 PM 23441136 ER PT J AU Shi, W Bain, AL Schwer, B Al-Ejeh, F Smith, C Wong, L Chai, H Miranda, MS Ho, U Kawaguchi, M Miura, Y Finnie, JW Wall, M Heierhorst, J Wicking, C Spring, KJ Alt, FW Khanna, KK AF Shi, Wei Bain, Amanda L. Schwer, Bjoern Al-Ejeh, Fares Smith, Corey Wong, Lee Chai, Hua Miranda, Mariska S. Ho, Uda Kawaguchi, Makoto Miura, Yutaka Finnie, John W. Wall, Meaghan Heierhorst, Jorg Wicking, Carol Spring, Kevin J. Alt, Frederick W. Khanna, Kum Kum TI Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2 SO PLOS GENETICS LA English DT Article ID REPLICATION PROTEIN-A; CLASS-SWITCH RECOMBINATION; COSTO-MANDIBULAR SYNDROME; ABNORMAL RIB DEVELOPMENT; DNA-DAMAGE RESPONSE; ATAXIA-TELANGIECTASIA; EPITHELIAL-CELLS; PROGENITOR CELLS; SECKEL-SYNDROME; MICE AB Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling and DNA double-strand break repair by homologous recombination. Here we report that germline Ssb1(-/-) embryos die at birth from respiratory failure due to severe rib cage malformation and impaired alveolar development, coupled with additional skeletal defects. Unexpectedly, Ssb1(-/-) fibroblasts did not exhibit defects in Atm signaling or gamma-H2ax focus kinetics in response to ionizing radiation (IR), and B-cell specific deletion of Ssb1 did not affect class-switch recombination in vitro. However, conditional deletion of Ssb1 in adult mice led to increased cancer susceptibility with broad tumour spectrum, impaired male fertility with testicular degeneration, and increased radiosensitivity and IR-induced chromosome breaks in vivo. Collectively, these results demonstrate essential roles of Ssb1 in embryogenesis, spermatogenesis, and genome stability in vivo. C1 [Shi, Wei; Bain, Amanda L.; Al-Ejeh, Fares; Smith, Corey; Miranda, Mariska S.; Ho, Uda; Spring, Kevin J.; Khanna, Kum Kum] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Bain, Amanda L.; Spring, Kevin J.; Khanna, Kum Kum] Griffith Univ, Sch Biomol & Phys Sci, Nathan, Qld 4111, Australia. [Schwer, Bjoern; Chai, Hua; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Schwer, Bjoern; Chai, Hua; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet & Pediat, Boston, MA USA. [Wong, Lee] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Miranda, Mariska S.; Spring, Kevin J.; Khanna, Kum Kum] Univ Queensland, Sch Med, Herston, Qld, Australia. [Kawaguchi, Makoto; Miura, Yutaka] Nagoya City Univ, Grad Sch Med Sci, Dept Bioregulat & Mol Neurobiol, Nagoya, Aichi, Japan. [Finnie, John W.] SA Pathol, Inst Med & Vet Sci, Adelaide, SA, Australia. [Wall, Meaghan] St Vincents Hosp, Victorian Canc Cytogenet Serv, Melbourne, Vic, Australia. [Wall, Meaghan; Heierhorst, Jorg] St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. [Heierhorst, Jorg] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Wicking, Carol] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. RP Shi, W (reprint author), Queensland Inst Med Res, Bramston Terrace, Herston, Qld 4006, Australia. EM kumkum.khanna@qimr.edu.au RI Bain, Amanda/B-4907-2013; Wong, Lee/H-9757-2012; Al-Ejeh, Fares/M-7032-2016; OI Bain, Amanda/0000-0002-4980-2114; Wong, Lee/0000-0002-4005-7330; Al-Ejeh, Fares/0000-0002-1553-0077; Wicking, Carol/0000-0002-7225-3803; Spring, Kevin/0000-0003-0601-924X FU National Health and Medical Research Council (NHMRC) Project [552472, 1031327]; National Institutes of Health [5R01AI077595, 5T32CA009382]; Victorian Government's Operational Infrastructure Support Program; NHMRC FX This work was supported by National Health and Medical Research Council (NHMRC) Project Grants 552472 and 1031327 (KKK), National Institutes of Health Grants 5R01AI077595 (FWA) and 5T32CA009382 (BS), and a Victorian Government's Operational Infrastructure Support Program (JH). KKK is an NHMRC Senior Principal Research Fellow; JH and CW are NHMRC Senior Research Fellows. FWA is an Investigator of the Howard Hughes Medical Institute. ALB is supported by an NHMRC Biomedical Postgraduate Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 16 Z9 16 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD FEB PY 2013 VL 9 IS 2 AR e1003298 DI 10.1371/journal.pgen.1003298 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 099RG UT WOS:000315638300049 PM 23408915 ER PT J AU Tomlinson, M Rotheram-Borus, MJ Swartz, L Tsai, AC AF Tomlinson, Mark Rotheram-Borus, Mary Jane Swartz, Leslie Tsai, Alexander C. TI Scaling Up mHealth: Where Is the Evidence? SO PLOS MEDICINE LA English DT Editorial Material ID DEVELOPING-COUNTRIES; RANDOMIZED-TRIAL; HEALTH BEHAVIORS; ADHERENCE; CARE; REMINDERS; INTERVENTIONS; COMMUNICATION; MESSAGES; PROGRAMS C1 [Tomlinson, Mark; Swartz, Leslie] Univ Stellenbosch, Dept Psychol, Ctr Publ Mental Hlth, ZA-7600 Stellenbosch, South Africa. [Rotheram-Borus, Mary Jane] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, MD Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Tomlinson, M (reprint author), Univ Stellenbosch, Dept Psychol, Ctr Publ Mental Hlth, ZA-7600 Stellenbosch, South Africa. EM markt@sun.ac.za RI Swartz, Leslie/A-5168-2008; OI Swartz, Leslie/0000-0003-1741-5897; Tsai, Alexander/0000-0001-6397-7917 FU NIMH NIH HHS [K23 MH-096620, K23 MH096620, P30 MH058107] NR 38 TC 119 Z9 121 U1 13 U2 55 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD FEB PY 2013 VL 10 IS 2 AR e1001382 DI 10.1371/journal.pmed.1001382 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 099BC UT WOS:000315592800004 PM 23424286 ER PT J AU Vimaleswaran, KS Berry, DJ Lu, C Tikkanen, E Pilz, S Hiraki, LT Cooper, JD Dastani, Z Li, R Houston, DK Wood, AR Michaelsson, K Vandenput, L Zgaga, L Yerges-Armstrong, LM McCarthy, MI Dupuis, J Kaakinen, M Kleber, ME Jameson, K Arden, N Raitakari, O Viikari, J Lohman, KK Ferrucci, L Melhus, H Ingelsson, E Byberg, L Lind, L Lorentzon, M Salomaa, V Campbell, H Dunlop, M Mitchell, BD Herzig, KH Pouta, A Hartikainen, AL Streeten, EA Theodoratou, E Jula, A Wareham, NJ Ohlsson, C Frayling, TM Kritchevsky, SB Spector, TD Richards, JB Lehtimaki, T Ouwehand, WH Kraft, P Cooper, C Marz, W Power, C Loos, RJF Wang, TJ Jarvelin, MR Whittaker, JC Hingorani, AD Hypponen, E AF Vimaleswaran, Karani S. Berry, Diane J. Lu, Chen Tikkanen, Emmi Pilz, Stefan Hiraki, Linda T. Cooper, Jason D. Dastani, Zari Li, Rui Houston, Denise K. Wood, Andrew R. Michaelsson, Karl Vandenput, Liesbeth Zgaga, Lina Yerges-Armstrong, Laura M. McCarthy, Mark I. Dupuis, Josee Kaakinen, Marika Kleber, Marcus E. Jameson, Karen Arden, Nigel Raitakari, Olli Viikari, Jorma Lohman, Kurt K. Ferrucci, Luigi Melhus, Hakan Ingelsson, Erik Byberg, Liisa Lind, Lars Lorentzon, Mattias Salomaa, Veikko Campbell, Harry Dunlop, Malcolm Mitchell, Braxton D. Herzig, Karl-Heinz Pouta, Anneli Hartikainen, Anna-Liisa Streeten, Elizabeth A. Theodoratou, Evropi Jula, Antti Wareham, Nicholas J. Ohlsson, Claes Frayling, Timothy M. Kritchevsky, Stephen B. Spector, Timothy D. Richards, J. Brent Lehtimaki, Terho Ouwehand, Willem H. Kraft, Peter Cooper, Cyrus Maerz, Winfried Power, Chris Loos, Ruth J. F. Wang, Thomas J. Jaervelin, Marjo-Riitta Whittaker, John C. Hingorani, Aroon D. Hyppoenen, Elina CA Genetic Invest Anthropometric Trai TI Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts SO PLOS MEDICINE LA English DT Article ID BODY-MASS INDEX; CARDIOVASCULAR-DISEASE RISK; GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; INSTRUMENTAL VARIABLES; D DEFICIENCY; 25-HYDROXYVITAMIN D; D INSUFFICIENCY; COMMON OBESITY; PREVALENCE AB Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. C1 [Vimaleswaran, Karani S.; Berry, Diane J.; Power, Chris; Hyppoenen, Elina] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Vimaleswaran, Karani S.; Berry, Diane J.; Power, Chris; Hyppoenen, Elina] UCL Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, London, England. [Lu, Chen; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tikkanen, Emmi] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Tikkanen, Emmi; Salomaa, Veikko; Jula, Antti] Natl Inst Hlth & Welf, Helsinki, Finland. [Pilz, Stefan] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria. [Pilz, Stefan] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Hiraki, Linda T.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Cooper, Jason D.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn Wellcome Trust Diabet & I, Cambridge, England. [Dastani, Zari] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada. [Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med, Montreal, PQ H3T 1E2, Canada. [Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. [Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol & Biostat, Montreal, PQ H3T 1E2, Canada. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA. [Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [Michaelsson, Karl; Byberg, Liisa] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Vandenput, Liesbeth; Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Inst Med, Dept Internal Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Zgaga, Lina; Campbell, Harry; Theodoratou, Evropi] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia. [Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Dupuis, Josee] NHLBI, Framingham, MA USA. [Kaakinen, Marika; Herzig, Karl-Heinz; Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Kaakinen, Marika; Herzig, Karl-Heinz; Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Kleber, Marcus E.] LURIC Study Non Profit LLC, Freiburg, Germany. [Kleber, Marcus E.] Heidelberg Univ, Mannheim Inst Publ Hlth, Mannheim Med Fac, Social & Prevent Med, Mannheim, Germany. [Jameson, Karen; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Arden, Nigel] Botnar Res Ctr, NIHR Musculoskeletal BRU, Oxford, England. [Arden, Nigel] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Raitakari, Olli; Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Lohman, Kurt K.] Wake Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Ferrucci, Luigi] Harbor Hosp, Clin Res Branch, Baltimore, MD USA. [Melhus, Hakan; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Dunlop, Malcolm] Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp & Acad Coloproctol, Edinburgh EH8 9YL, Midlothian, Scotland. [Dunlop, Malcolm] Western Gen Hosp Edinburgh, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Herzig, Karl-Heinz] Univ Oulu, Inst Biomed, Oulu, Finland. [Herzig, Karl-Heinz] Kuopio Univ Hosp, Dept Psychiat, SF-70210 Kuopio, Finland. [Pouta, Anneli] Univ Oulu, Dept Publ Hlth Sci & Gen Practice, Oulu, Finland. [Hartikainen, Anna-Liisa] Univ Oulu, Dept Obstet & Gynaecol & Publ Hlth & Gen Practice, Oulu, Finland. [Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Spector, Timothy D.; Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England. [Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Cambridge, England. [Ouwehand, Willem H.] NHS Blood & Transplant, Cambridge, England. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth, Mannheim Med Fac, Social & Prevent Med, Mannheim, Germany. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth,Fac Med, London, England. [Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland. [Whittaker, John C.] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England. [Whittaker, John C.] GlaxoSmithKline, Quantitat Sci, Stevenage, Herts, England. [Hingorani, Aroon D.] UCL, Div Populat Hlth, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England. [Hingorani, Aroon D.] UCL, Div Med, Ctr Clin Pharmacol, London, England. RP Vimaleswaran, KS (reprint author), UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. EM e.hypponen@ucl.ac.uk RI Smith, Albert Vernon/K-5150-2015; Aben, Katja/G-9686-2016; Rudan, Igor/I-1467-2012; kinnunen, leena/B-7059-2012; Visvikis-Siest, Sophie/H-2324-2014; Dunlop, Malcolm/F-1973-2011; Beckmann, Jacques S /A-9772-2008; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Colaus, PsyColaus/K-6607-2013; Hypponen, Elina/B-2596-2014; Lu, Chen/D-8514-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Theodoratou, Evropi/C-3430-2014; Kiemeney, Lambertus/D-3357-2009; Aspelund, Thor/C-5983-2008; Palmer, Lyle/K-3196-2014; Witte, Daniel/C-1722-2008 OI Pichler, Irene/0000-0001-8251-0757; Magi, Reedik/0000-0002-2964-6011; Lango Allen, Hana/0000-0002-7803-8688; Esko, Tonu/0000-0003-1982-6569; Smith, Albert Vernon/0000-0003-1942-5845; Zgaga, Lina/0000-0003-4089-9703; Dupuis, Josee/0000-0003-2871-3603; Kritchevsky, Stephen/0000-0003-3336-6781; Luben, Robert/0000-0002-5088-6343; Scherag, Andre/0000-0002-9406-4704; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vandenput, Liesbeth/0000-0002-1712-6131; Aben, Katja/0000-0002-0214-2147; Rudan, Igor/0000-0001-6993-6884; kinnunen, leena/0000-0001-8739-4812; Visvikis-Siest, Sophie/0000-0001-8104-8425; Dunlop, Malcolm/0000-0002-3033-5851; Beckmann, Jacques S /0000-0002-9741-1900; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Thiering, Elisabeth/0000-0002-5429-9584; Kaakinen, Marika/0000-0002-9228-0462; Karani, Vimal/0000-0002-8485-8930; Jorgensen, Torben/0000-0001-9453-2830; Mitchell, Braxton/0000-0003-4920-4744; Ouwehand, Willem/0000-0002-7744-1790; Lawlor, Debbie A/0000-0002-6793-2262; Hattersley, Andrew/0000-0001-5620-473X; de Geus, Eco/0000-0001-6022-2666; Kleber, Marcus/0000-0003-0663-7275; Hypponen, Elina/0000-0003-3670-9399; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862; Theodoratou, Evropi/0000-0001-5887-9132; Kiemeney, Lambertus/0000-0002-2368-1326; Aspelund, Thor/0000-0002-7998-5433; Palmer, Lyle/0000-0002-1628-3055; Witte, Daniel/0000-0002-0769-2922 FU British Heart Foundation [PG/09/023]; UK Medical Research Council (MRC) [G0601653]; British Heart Foundation Senior Research Fellow(Award) [FS05/125]; MRC Centre of Epidemiology for Child Health; NHS Executive; Canada Institute of Research (CIHR) Fellowship award; Amgen; Eli Lilly; Medtronic; Merck; Novartis; Servier FX The authors thank the British Heart Foundation (grant PG/09/023) and the UK Medical Research Council (MRC; grant G0601653) for funding this work. ADH is a British Heart Foundation Senior Research Fellow (Award FS05/125). EH is a Department of Health (UK) Public Health Career Scientist. This work was undertaken at the Centre for Paediatric Epidemiology and Biostatistics, which benefits from funding support from the MRC in its capacity as the MRC Centre of Epidemiology for Child Health. Research at the University College London Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; LTH is currently supported by a Canada Institute of Research (CIHR) Fellowship award. CC has received honoraria and consulting fees from Amgen, Eli Lilly, Medtronic, Merck, Novartis, and Servier. WM is an employee of synlab laboratory services GmbH. Synlab offers vitamin D testing. TJW is on the scientific advisory board for Diasorin Inc. and has received research support from them. JCW is 90% employed by GlaxoSmithKline (GSK) whilst maintaining a 10% appointment at London School of Hygiene & Tropical Medicine (LSHTM), and holds GSK shares. All other authors declare that no competing interests exist. NR 50 TC 206 Z9 212 U1 4 U2 80 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD FEB PY 2013 VL 10 IS 2 AR e1001383 DI 10.1371/journal.pmed.1001383 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 099BC UT WOS:000315592800005 PM 23393431 ER PT J AU Eriksson, S Graf, EH Dahl, V Strain, MC Yukl, SA Lysenko, ES Bosch, RJ Lai, J Chioma, S Emad, F Abdel-Mohsen, M Hoh, R Hecht, F Hunt, P Somsouk, M Wong, J Johnston, R Siliciano, RF Richman, DD O'Doherty, U Palmer, S Deeks, SG Siliciano, JD AF Eriksson, Susanne Graf, Erin H. Dahl, Viktor Strain, Matthew C. Yukl, Steven A. Lysenko, Elena S. Bosch, Ronald J. Lai, Jun Chioma, Stanley Emad, Fatemeh Abdel-Mohsen, Mohamed Hoh, Rebecca Hecht, Frederick Hunt, Peter Somsouk, Ma Wong, Joseph Johnston, Rowena Siliciano, Robert F. Richman, Douglas D. O'Doherty, Una Palmer, Sarah Deeks, Steven G. Siliciano, Janet D. TI Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; LOW-LEVEL VIREMIA; LATENT HIV-1; IN-VIVO; INFECTED INDIVIDUALS; PERIPHERAL-BLOOD; PLASMA VIREMIA AB HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART). The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+) T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+) T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+) T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy between infected cell frequencies measured by viral outgrowth versus PCR assays is an urgent priority in HIV-1 cure research. C1 [Eriksson, Susanne; Dahl, Viktor; Palmer, Sarah] Swedish Inst Communicable Dis, Dept Diagnost & Vaccinol, Solna, Sweden. [Eriksson, Susanne; Dahl, Viktor; Palmer, Sarah] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden. [Graf, Erin H.; Lysenko, Elena S.; O'Doherty, Una] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Strain, Matthew C.; Richman, Douglas D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Strain, Matthew C.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Yukl, Steven A.; Wong, Joseph] San Francisco VA Med Ctr, San Francisco, CA USA. [Yukl, Steven A.; Abdel-Mohsen, Mohamed; Hoh, Rebecca; Hecht, Frederick; Hunt, Peter; Somsouk, Ma; Wong, Joseph; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lai, Jun; Chioma, Stanley; Emad, Fatemeh; Siliciano, Robert F.; Siliciano, Janet D.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Johnston, Rowena] Fdn AIDS Res, AmfAR, New York, NY USA. [Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Eriksson, S (reprint author), Swedish Inst Communicable Dis, Dept Diagnost & Vaccinol, Solna, Sweden. EM jsilicia@jhmi.edu OI Dahl, Viktor/0000-0001-9921-5172 FU ARCHE Collaborative Research Grant from the Foundation for AIDS Research [amFAR 108165-50-RGRL]; Martin Delaney CARE and DARE Collaboratories(NIH) [AI096113, 1U19AI096109]; NIH [43222]; Howard Hughes Medical Institute; Department of Veterans Affairs [1 IK2 CX000520-01]; James Pendleton Charitable Trust; National Institutes of Health [AI 080193, AI74621, AI69432-S]; CFAR [AI306214]; NIAID [RO1AIO87145, K24AIO69994]; UCSF/Gladstone CFAR [P30 AIO27763]; UCSF Clinical and Translational Research Institute Clinical Research Center [UL 1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246] FX This work was supported by an ARCHE Collaborative Research Grant from the Foundation for AIDS Research (amFAR 108165-50-RGRL), by the Martin Delaney CARE and DARE Collaboratories(NIH grants AI096113 and 1U19AI096109), and by NIH grant 43222 (RFS), and by the Howard Hughes Medical Institute (RFS). For MS and DDR, this work was supported by the Department of Veterans Affairs, the James Pendleton Charitable Trust, National Institutes of Health (AI 080193, AI74621, AI69432-S), and CFAR grant AI306214. For SAY, this work was supported by the Department of Veterans Affairs (VA Career Development Award 1 IK2 CX000520-01). The UCSF SCOPE cohort was supported in part by the NIAID (RO1AIO87145, K24AIO69994), the UCSF/Gladstone CFAR (P30 AIO27763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL 1 RR024131) and the Center for AIDS Prevention Studies (P30 MH62246). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 155 Z9 156 U1 5 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2013 VL 9 IS 2 AR e1003174 DI 10.1371/journal.ppat.1003174 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 099UU UT WOS:000315648900024 PM 23459007 ER PT J AU Chan, ED Iseman, MD AF Chan, Edward D. Iseman, Michael D. TI Underlying Host Risk Factors for Nontuberculous Mycobacterial Lung Disease SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Marfan syndrome; environmental mycobacteria; bronchiectasis; pectus excavatum; scoliosis; nontuberculous mycobacteria ID PULMONARY ALVEOLAR PROTEINOSIS; ANTITUMOR NECROSIS FACTOR; RAPIDLY GROWING MYCOBACTERIA; CHRONIC MYELOGENOUS LEUKEMIA; WILLIAMS-CAMPBELL-SYNDROME; AVIUM COMPLEX DISEASE; MITRAL-VALVE-PROLAPSE; MOUNIER-KUHN-SYNDROME; AFRICAN GOLD MINERS; GROWTH-FACTOR-BETA AB Nontuberculous mycobacteria (NTM) are environmental microbes that cause a variety of human diseases, particularly chronic lung infections. Despite the fact that NTM are widespread in the environment, relatively few people develop NTM lung disease, suggesting intrinsic vulnerability in some individuals. This paper reviews the evidence that underlying disorders predispose to NTM lung disease, in particular primary conditions that result in bronchiectasis, chronic obstructive pulmonary disease, alpha-1-antitrypsin anomalies, pneumoconiosis, pulmonary alveolar proteinosis, and frank immunosuppressive states such as that associated with the use of anti-tumor necrosis factor-alpha biologics, posttransplantation immunosuppression, and HIV infection. Over the past several decades, NTM lung disease has been increasingly identified in postmenopausal women with slender body habitus. Thus we will also review the clinical and experimental evidence which supports the observation that such individuals are predisposed to NTM lung disease. C1 [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.; Iseman, Michael D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chan, Edward D.] Natl Jewish Hlth, Cell Biol Program, Denver, CO 80206 USA. [Chan, Edward D.; Iseman, Michael D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Iseman, Michael D.] Univ Colorado Denver, Div Infect Dis, Denver, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 139 TC 34 Z9 35 U1 0 U2 8 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD FEB PY 2013 VL 34 IS 1 BP 110 EP 123 DI 10.1055/s-0033-1333573 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 101RY UT WOS:000315793300011 PM 23460011 ER PT J AU Granda, ML Carlin, SM Moseley, CK Neelamegam, R Mandeville, JB Hooker, JM AF Granda, Michael L. Carlin, Stephen M. Moseley, Christian K. Neelamegam, Ramesh Mandeville, Joseph B. Hooker, Jacob M. TI Synthesis and Evaluation of Methylated Arylazepine Compounds for PET Imaging of 5-HT2c Receptors SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Serotonin; PET imaging; carbon-11; 5-HT2c agonist ID SEROTONIN RECEPTORS; HUMAN-BRAIN; RECOGNITION SITES; LOCALIZATION; BINDING; BEHAVIOR; AGONIST AB The serotonin 5-HT2c receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT2c in these diseases, a method for measuring 5-HT2c density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT2c but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT2c ligands, may be a suitable method for producing new radiotracers for 5-HT2c. The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 +/- 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT2c ligands as radiotracers for PET. C1 [Granda, Michael L.; Carlin, Stephen M.; Moseley, Christian K.; Neelamegam, Ramesh; Mandeville, Joseph B.; Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Hooker, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 FU National Institute of Health [1R21MH093874] FX This project was funded by a grant from the National Institute of Health (1R21MH093874). NR 21 TC 8 Z9 9 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD FEB PY 2013 VL 4 IS 2 BP 261 EP 265 DI 10.1021/cn300223d PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 095HT UT WOS:000315326000007 PM 23421677 ER PT J AU Koido, S Gong, JL AF Koido, Shigeo Gong, Jianlin TI Characterization of Structure and Direct Antigen Presentation by Dendritic/Tumor-fused Cells as Cancer Vaccines SO ANTICANCER RESEARCH LA English DT Article DE Dendritic cell; cancer vaccine; antigen presentation; fusion ID CYTOTOXIC T-LYMPHOCYTES; HUMAN TUMOR-ANTIGEN; CLASS-II MOLECULES; ANTITUMOR IMMUNITY; CARCINOMA-CELLS; IN-VIVO; FUSION CELLS; VACCINATION; INDUCTION; ELECTROFUSION AB Background: Previous work has shown that fusion of dendritic cells (DCs) and tumor cells induces potent antitumor immune responses. However, little is known on whether fused cells directly present tumor-associated antigens (TAAs) through major histocompatibility complex (MHC) class I and II pathways in the context of co-stimulatory molecules. Materials and Methods: Fusion cells were generated between DCs and MC38 carcinoma cells stably expressing mucin-1 (MUC1) by polyethylene glycol. The characterization of structure and antigen presentation by fused cells was examined by immunoelectron microscopic and flow cytometric analyses. Results: The cytoplasm from both cellular entities was integrated, while their nuclei were independently preserved. Short-term culture gave fused cells sufficient time to integrate and directly display MUC1 through MHC class I and II pathways in the context of co-stimulatory molecules. Conclusion: DC-derived molecules and TAAs are presumably synthesized at separate sites of fused cells, to converge and complex with each other. C1 [Gong, Jianlin] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Koido, Shigeo] Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kashiwa, Chiba 2778564, Japan. [Koido, Shigeo; Gong, Jianlin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Koido, S (reprint author), Jikei Univ, Sch Med, Dept Gastroenterol & Hepatol, 163-1 Kashiwa Shita, Kashiwa, Chiba 2778564, Japan. EM shigeo_koido@jikei.ac.jp FU National Cancer Institute Grant [R01 CA87057]; US Department of Defense Breast Cancer Research programs [990344]; Susan G. Komen Breast Cancer Foundation [9825]; Ministry of Education, Cultures, Sports, Science and Technology of Japan FX This work was supported by National Cancer Institute Grant R01 CA87057; by the US Department of Defense Breast Cancer Research programs, grant 990344; by the Susan G. Komen Breast Cancer Foundation, grant 9825; and by Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Cultures, Sports, Science and Technology of Japan. NR 36 TC 11 Z9 11 U1 1 U2 15 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD FEB PY 2013 VL 33 IS 2 BP 347 EP 354 PG 8 WC Oncology SC Oncology GA 096SG UT WOS:000315424000001 PM 23393323 ER PT J AU Yasuda, Y Fukushima, Y Kaneki, M Martyn, JAJ AF Yasuda, Yoshikazu Fukushima, Yuji Kaneki, Masao Martyn, J. A. Jeevendra TI Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Glucose output (hepatic); Hepatic glucose uptake; Hyperinsulinemic clamp; Insulin resistance; Muscle glucose uptake; Propofol; Sedation ID CRITICALLY-ILL PATIENTS; INFUSION SYNDROME; CRITICAL ILLNESS; GLUCOSE CONTROL; MITOCHONDRIAL RESPIRATION; DIABETIC-PATIENTS; THERAPY; HYPERGLYCEMIA; METABOLISM; MECHANISMS AB Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [H-3]glucose and 2-deoxy[C-14]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats. (C) 2012 Elsevier Inc. All rights reserved. C1 [Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J. A. Jeevendra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med,Shriners Ho, Boston, MA 02114 USA. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med,Shriners Ho, 51 Blossom St,Room 206, Boston, MA 02114 USA. EM jmartyn@partners.org FU National Institutes of Health [R01-GM 055082, P50-GM-2500]; Shriners Hospitals for Children(R) Research Philanthropy FX This study was supported in part by grants to JAJM from the National Institutes of Health R01-GM 055082 and P50-GM-2500 Project I, and from the Shriners Hospitals for Children (R) Research Philanthropy. NR 46 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 1 PY 2013 VL 431 IS 1 BP 81 EP 85 DI 10.1016/j.bbrc.2012.12.084 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 096UC UT WOS:000315428800015 PM 23274498 ER PT J AU Trivedi, MH Morris, DW Wisniewski, SR Nierenberg, AA Gaynes, BN Kurian, BT Warden, D Stegman, D Shores-Wilson, K Rush, AJ AF Trivedi, Madhukar H. Morris, David W. Wisniewski, Stephen R. Nierenberg, Andrew A. Gaynes, Bradley N. Kurian, Benji T. Warden, Diane Stegman, Diane Shores-Wilson, Kathy Rush, A. John TI Clinical and Sociodemographic Characteristics Associated With Suicidal Ideation in Depressed Outpatients SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE suicidal ideation; depression; major depressive disorder; anxiety; suicide assessment ID SEQUENCED TREATMENT ALTERNATIVES; NATIONAL-COMORBIDITY-SURVEY; INTERACTIVE VOICE RESPONSE; ILLNESS RATING-SCALE; STAR-ASTERISK-D; REPORT QIDS-SR; MAJOR DEPRESSION; PSYCHIATRIC OUTPATIENTS; RISK-FACTORS; SELF-REPORT AB Objective: To identify clinical and sociodemographic characteristics associated with suicidal ideation (SI) among patients seeking care for depression in routine primary and psychiatric care settings. Methods: We examined data from 4041 treatment-seeking outpatients with major depressive disorder (MDD) to compare baseline sociodemographic and clinical characteristics of those with and without SI, and the presence or absence of baseline depressive symptoms and psychiatric comorbidities in those with SI. Results: SI was significantly (P < 0.01) associated with numerous sociodemographic characteristics (that is, lower level of education, Caucasian or African American, male, unemployed, and treated in psychiatric care) and clinical features (that is, previous suicide attempt, younger age of MDD onset, greater baseline depressive symptom severity, greater number of depressive symptoms, and presence of agoraphobia and [or] generalized anxiety disorder). Elevated levels of SI at baseline were associated with decreased remission rates. Conclusions: Consistent with past findings, increased rates of SI were associated with greater depressive symptom severity as well as other features suggestive of severity of illness. Our results confirm previous findings of associations between SI and panic and (or) phobic symptoms and anxiety, but did not confirm previous findings of an association between SI and alcohol or drug use and (or) dependence. While selective serotonin reuptake inhibitor monotherapy appeared significantly helpful in reducing SI during the course of treatment, the presence of SI at baseline was found to be a associated with decreased treatment response, with patients reporting SI at the start of treatment being less likely to achieve remission. C1 [Trivedi, Madhukar H.; Morris, David W.; Kurian, Benji T.; Warden, Diane; Stegman, Diane; Shores-Wilson, Kathy] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Clin & Res Program, Boston, MA 02114 USA. [Gaynes, Bradley N.] Univ N Carolina, Chapel Hill, NC USA. [Rush, A. John] Duke Natl Univ Singapore, Off Clin Sci, Singapore, Singapore. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health (NIMH); National Institutes of Health [N01MH90003]; Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc; Cyberonics, Inc; Merck; National Alliance for Research in Schizophrenia and Depression; NIMH; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix Pharmaceuticals (Epix); Solvay Pharmaceuticals, Inc; Targacept; Abbott Laboratories, Inc; Abdi Ibrahim; Akzo (Organon Pharmaceuticals Inc); Alkermes; AstraZeneca; Axon Advisors; Bristol-Myers Squibb Company; Cephalon, Inc; Evotec; Fabre Kramer Pharmaceuticals, Inc; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products; Johnson Johnson PRD; Libby; LP; Eli Lilly Company; Lundbeck; Meade Johnson; MedAvante; Medtronic; Naurex; Neuronetics; Otsuka Pharmaceuticals, Pamlab; Parke-Davis Pharmaceuticals, Inc; Pfizer Inc; Ppd-lealth; Rexahn Pharmaceuticals; Sepracor; SHIRE Development; Sierra; Takeda; Tal Medical/Puretech; Transcept; VantagePoint; Wyeth-Ayerst Laboratories; Otsuka Pharmaceutical Co Ltd; University of Michigan; Brain Resource Ltd; Singapore College of Family Physicians; Guilford Publications and University of Texas Southwestern Medical Center; International College of Neuropsychopharmacology; NEVIH; Duke-NUS; Targacept, Inc; Pfizer, Inc; Johnson Johnson; Rexahn FX This project was funded by the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (Principal Investigator, Dr Rush). Neither the content of this publication nor the mention of trade names, commercial products, or organizations, necessarily reflects the views or policies of the Department of Health and Human Services or imply endorsement by the US Government. We acknowledge the editorial assistance of Jon Kilner.; Dr Trivedi has received research support from the Agency for Healthcare Research and Quality, Corcept Therapeutics, Inc, Cyberonics, Inc, Merck, National Alliance for Research in Schizophrenia and Depression, NIMH, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Solvay Pharmaceuticals, Inc, and Targacept, and consulting and speaker fees from Abbott Laboratories, Inc, Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc, Evotec, Fabre Kramer Pharmaceuticals, Inc, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, LP, Eli Lilly & Company, Lundbeck, Meade Johnson, MedAvante, Medtronic, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc, Pfizer Inc, Ppd-lealth, Rexahn Pharmaceuticals, Sepracor, SHIRE Development, Sierra, Takeda, Tal Medical/Puretech, Transcept, VantagePoint, and Wyeth-Ayerst Laboratories. Dr Wisniewski has been a consultant for Cyberonics, Inc, ImaRx Therapeutics, Inc, Bristol-Myers Squibb Company, Organon, Case-Western University, Singapore Clinical Research Institute, Dey Pharmaceuticals, and Venebio Group LLC.; Dr Rush has received consultant fees from Otsuka Pharmaceutical Co Ltd, University of Michigan, Brain Resource Ltd; speaking fees from Singapore College of Family Physicians; royalties from Guilford Publications and University of Texas Southwestern Medical Center; travel grant from the International College of Neuropsychopharmacology; and research support from NEVIH and Duke-NUS.; Dr Kurian has received research support from Targacept, Inc, Pfizer, Inc, Johnson & Johnson, Evotec, Rexahn, Naurex, Forest Pharmaceuticals, and NIMH. NR 52 TC 5 Z9 5 U1 3 U2 12 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD FEB PY 2013 VL 58 IS 2 BP 113 EP 122 PG 10 WC Psychiatry SC Psychiatry GA 095HA UT WOS:000315324100009 PM 23442899 ER PT J AU Garcia-Albeniz, X Nan, HM Valeri, L Morikawa, T Kuchiba, A Phipps, AI Hutter, CM Peters, U Newcomb, PA Fuchs, CS Giovannucci, EL Ogino, S Chan, AT AF Garcia-Albeniz, Xabier Nan, Hongmei Valeri, Linda Morikawa, Teppei Kuchiba, Aya Phipps, Amanda I. Hutter, Carolyn M. Peters, Ulrike Newcomb, Polly A. Fuchs, Charles S. Giovannucci, Edward L. Ogino, Shuji Chan, Andrew T. TI Phenotypic and tumor molecular characterization of colorectal cancer in relation to a susceptibility SMAD7 variant associated with survival SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; ISLAND METHYLATOR PHENOTYPE; BODY-MASS INDEX; COLON-CANCER; MICROSATELLITE INSTABILITY; PATHOLOGICAL EPIDEMIOLOGY; RISK; LOCI; METAANALYSIS; EXPRESSION AB The minor allele (G) of rs4939827, a SMAD7 (18q21) intronic variant, is associated with a lower risk of developing colorectal cancer (CRC) and poorer survival after diagnosis. Our objective was to evaluate the associations of this variant with different tumor phenotype and intratumoral molecular characteristics. We evaluated 1509 CRC cases and 2307 age-matched controls nested within the Nurses' Health Study and the Health Professionals Follow-up Study. We used the TaqMan assay to genotype rs4939827 and logistic regression to assess the association of rs4939827 with risk of CRC according to different phenotypic and molecular characteristics. We found that the minor allele (G) in rs4939827 (SMAD7, 18q21) was associated with a lower risk of developing tumor stage pT1 or pT2 CRC [multivariate odds ratio (OR), 0.73; 95% confidence interval (CI) 0.62-0.87] but not tumor stage pT3 or pT4 (multivariate OR, 1.07; 95% CI 0.93-1.23, P for heterogeneity = 1.2 x 10(-4)). The association between rs4939827 and CRC also significantly differed by methylation of RUNX3 (P for heterogeneity = 0.005). Among those with CRC, the minor allele (G) in rs4939827 was significantly associated with poorer overall survival (hazards ratio, 1.20; 95% CI, 1.02-1.42). We can conclude that the minor allele (G) of the germline intronic SMAD7 variant rs4939827 is associated with a lower risk of CRC with earlier tumor stage and CRC without methylation of the tumor suppressor RUNX3. These findings suggest that individuals with this SMAD7 variant that develop CRC are more probably to have tumors with greater invasiveness and methylation of RUNX3, which potentially contributes to their poorer observed survival. C1 [Garcia-Albeniz, Xabier; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Garcia-Albeniz, Xabier; Nan, Hongmei; Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Garcia-Albeniz, Xabier; Nan, Hongmei; Morikawa, Teppei; Kuchiba, Aya; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nan, Hongmei] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Canc Epidemiol, Baltimore, MD 21201 USA. [Valeri, Linda] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Morikawa, Teppei; Ogino, Shuji] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Morikawa, Teppei; Kuchiba, Aya; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kuchiba, Aya; Giovannucci, Edward L.] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA. [Phipps, Amanda I.; Hutter, Carolyn M.; Peters, Ulrike; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chan, AT (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM achan@partners.org FU National Institutes of Health (NIH) / National Cancer Institute (NCI) [CA137178, CA059045, CA151993, CA055075, CA087969, CA127003, CA094880, CA154337]; 'La Caixa' fellowship FX National Institutes of Health (NIH) / National Cancer Institute (NCI) (grant CA137178, CA059045, CA151993, CA055075, CA087969, CA127003, CA094880, CA154337); 'La Caixa' fellowship to X. G. A.; A. T. C. is a Damon Runyon Cancer Foundation Clinical Investigator. NR 39 TC 12 Z9 12 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2013 VL 34 IS 2 BP 292 EP 298 DI 10.1093/carcin/bgs335 PG 7 WC Oncology SC Oncology GA 099NH UT WOS:000315627900007 PM 23104301 ER PT J AU Steenkamp, MM Litz, BT AF Steenkamp, Maria M. Litz, Brett T. TI Psychotherapy for military-related posttraumatic stress disorder: Review of the evidence SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE PTSD; Combat; Military; War; Psychotherapy; Treatment ID PROLONGED EXPOSURE THERAPY; COGNITIVE PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH TREATMENT; PRIMARY-CARE; COMBAT VETERANS; PSYCHOLOGICAL TREATMENTS; SERVICE MEMBERS; NATIONAL-GUARD; BEHAVIORAL ACTIVATION AB Approximately 20% of the two million troops who have deployed to Iraq and Afghanistan may require treatment for posttraumatic stress disorder (PTSD). We review treatment outcome studies on individual outpatient therapy for military-related PTSD, and consider the extent to which veterans initiate and complete available PTSD treatments. We conclude with considerations for future research. Published by Elsevier Ltd. C1 [Steenkamp, Maria M.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Steenkamp, Maria M.; Litz, Brett T.] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Steenkamp, MM (reprint author), Boston Vet Affairs Med Ctr, 150 S Huntington Ave,13B-73, Boston, MA 02130 USA. EM maria.steenkamp2@va.gov NR 81 TC 44 Z9 46 U1 0 U2 45 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD FEB PY 2013 VL 33 IS 1 BP 45 EP 53 DI 10.1016/j.cpr.2012.10.002 PG 9 WC Psychology, Clinical SC Psychology GA 083RJ UT WOS:000314482600004 PM 23123570 ER PT J AU Alcantara, C Casement, MD Lewis-Fernandez, R AF Alcantara, Cantlela Casement, Melynda D. Lewis-Fernandez, Roberto TI Conditional risk for PTSD among Latinos: A systematic review of racial/ethnic differences and sociocultural explanations SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE PTSD; Hispanics; Immigrants; Mental health; Psychosocial risk factors; Trauma ID POSTTRAUMATIC-STRESS-DISORDER; ATAQUES-DE-NERVIOS; NATIONAL COMORBIDITY SURVEY; INTIMATE PARTNER VIOLENCE; UNITED-STATES; ETHNIC-DIFFERENCES; ANXIETY SENSITIVITY; GENDER-DIFFERENCES; TERRORIST ATTACKS; VIETNAM VETERANS AB Conditional risk for Posttraumatic Stress Disorder (PTSD)-defined as prevalence, onset, persistence, or severity of PTSD after traumatic exposure appears to be higher among Latinos relative to non-Latinos after accounting for sociodemographic factors. This systematic review focuses on differences in conditional risk for PTSD between Latinos and non-Latinos (White, Black, or combined) and across Latino subgroups in studies that adjust for trauma exposure. We discuss methodological characteristics of existing articles and sociocultural explanatory factors. Electronic bibliographic searches were conducted for English-language articles published in peer-reviewed journals between 1991 and 2012. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-eight articles met inclusion criteria. Consistent support was found for elevated rates of PTSD onset and PTSD severity among Latinos relative to non-Latino Whites. The evidence on racial/ethnic differences in conditional risk for PTSD prevalence and PTSD persistence is mixed. Twenty-four articles evaluated sociocultural explanations, with the strongest support found for racial/ethnic variation in pen-traumatic responses and structure of PTSD. There were also consistent main effects for social disadvantage in studies that simultaneously adjusted for effects of race/ethnicity. Future research should use theoretically-driven models to formally test for interactions between sociocultural factors, race/ethnicity, and PTSD probability. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Alcantara, Cantlela] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Casement, Melynda D.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Casement, Melynda D.] Boston Univ, Med Ctr, Boston, MA USA. [Lewis-Fernandez, Roberto] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Alcantara, C (reprint author), Columbia Univ, Dept Med, Med Ctr, Ctr Behav Cardiovasc Hlth, PH-9,Room 9-319,622 W 168th St, New York, NY 10032 USA. EM ca2543@columbia.edu OI Casement, Melynda/0000-0002-5906-0994 FU NIMH NIH HHS [T32 MH019836, T32-MH019836, R01 MH072833, R01 MH077226] NR 67 TC 18 Z9 18 U1 6 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD FEB PY 2013 VL 33 IS 1 BP 107 EP 119 DI 10.1016/j.cpr.2012.10.005 PG 13 WC Psychology, Clinical SC Psychology GA 083RJ UT WOS:000314482600009 PM 23159328 ER PT J AU Marshall, J Shapiro, GI Uttenreuther-Fischer, M Ould-Kaci, M Stopfer, P Gordon, MS AF Marshall, John Shapiro, Geoffrey I. Uttenreuther-Fischer, Martina Ould-Kaci, Mahmoud Stopfer, Peter Gordon, Michael S. TI Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer SO FUTURE ONCOLOGY LA English DT Article DE afatinib; docetaxel; ErbB family blocker; pharmacokinetics; Phase I ID CELL LUNG-CANCER; ADVANCED SOLID TUMORS; 1ST-LINE TREATMENT; BREAST-CANCER; BIBW 2992; KINASE INHIBITOR; TYROSINE KINASE; OPEN-LABEL; TRIAL; EGFR AB Aims: To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. Patients & methods: The MTD was determined from dose-limiting toxicities in the first cycle. Results: Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients. Conclusion: Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile. C1 [Marshall, John] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Uttenreuther-Fischer, Martina; Stopfer, Peter] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. [Ould-Kaci, Mahmoud] Boehringer Ingelheim GmbH & Co KG, F-75013 Paris, France. [Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ 85258 USA. RP Marshall, J (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM marshalj@georgetown.edu FU Boehringer Ingelheim; Ogilvy Healthworld FX The clinical research involved in the production of this manuscript is sponsored by Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.; Writing assistance was utilized in the production of this manuscript. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Ogilvy Healthworld, with edits and suggestions by ML Hartley of the Lombardi Cancer Center, during the preparation of this article. NR 36 TC 16 Z9 16 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD FEB PY 2013 VL 9 IS 2 BP 271 EP 281 DI 10.2217/FON.12.195 PG 11 WC Oncology SC Oncology GA 093BD UT WOS:000315165800018 PM 23414476 ER PT J AU Keating, A DaSilva, G Perez, WS Gupta, V Cutler, CS Ballen, KK Cairo, MS Camitta, BM Champlin, RE Gajewski, JL Lazarus, HM Lill, M Marks, DI Nabhan, C Schiller, GJ Socie, G Szer, J Tallman, MS Weisdorf, DJ AF Keating, Armand DaSilva, Gisela Perez, Waleska S. Gupta, Vikas Cutler, Corey S. Ballen, Karen K. Cairo, Mitchell S. Camitta, Bruce M. Champlin, Richard E. Gajewski, James L. Lazarus, Hillard M. Lill, Michael Marks, David I. Nabhan, Chadi Schiller, Gary J. Socie, Gerald Szer, Jeffrey Tallman, Martin S. Weisdorf, Daniel J. TI Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research SO HAEMATOLOGICA LA English DT Article ID BONE-MARROW; COOPERATIVE-GROUP; MYELODYSPLASTIC-SYNDROME; COMPETING RISKS; OLDER PATIENTS; AML-10 TRIAL; CHEMOTHERAPY; SURVIVAL; THERAPY; RELAPSE AB The optimal post-remission treatment for acute myeloid leukemia in first complete remission remains uncertain. Previous comparisons of autologous versus allogeneic hematopoietic cell transplantation noted higher relapse, but lower treatment-related mortality though using bone marrow grafts, with treatment-related mortality of 12-20%. Recognizing lower treatment-related mortality using autologous peripheral blood grafts, in an analysis of registry data from the Center for International Blood and Transplant Research, we compared treatment-related mortality, relapse, leukemia-free survival, and overall survival for patients with acute myeloid leukemia in first complete remission (median ages 36-44, range 19-60) receiving myeloablative HLA-matched sibling donor grafts (bone marrow, n=475 or peripheral blood, n=428) versus autologous peripheral blood (n=230). The 5-year cumulative incidence of treatment-related mortality was 19% (95% confidence interval, 16-23%), 20% (17-24%) and 8% (5-12%) for allogeneic bone marrow, allogeneic peripheral blood and autologous peripheral blood stem cell transplant recipients, respectively. The corresponding figures for 5-year cumulative incidence of relapse were 20% (17-24%), 26% (21-30%) and 45% (38-52%), respectively. At 5 years, leukemia-free survival and overall survival rates were similar: allogeneic bone marrow 61% (56-65%) and 64% (59-68%); allogeneic peripheral blood 54% (49-59%) and 59% (54-64%); autologous peripheral blood 47% (40-54%) and 54% (47-60%); P=0.13 and P=0.19, respectively. In multivariate analysis the incidence of treatment-related mortality was lower after autologous peripheral blood transplantation than after allogeneic bone marrow/peripheral blood transplants [relative risk 0.37 (0.20-0.69); P=0.001], but treatment failure (death or relapse) after autologous peripheral blood was significantly more likely [relative risk 1.32 (1.06-1.64); P=0.011]. The 5-year overall survival, however, was similar in patients who received autologous peripheral blood (n=230) [relative risk 1.23 (0.98-1.55); P=0.071] or allogeneic bone marrow/peripheral blood (n=903). In the absence of an HLA-matched sibling donor, autologous peripheral blood may provide acceptable alternative post-remission therapy for patients with acute myeloid leukemia in first complete remission. C1 [Keating, Armand; Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Toronto, ON M5S 1A1, Canada. [DaSilva, Gisela] Univ Sao Paulo, Sao Paulo, Brazil. [Perez, Waleska S.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gajewski, James L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Nabhan, Chadi] Adv Lutheran Gen Hosp, Park Ridge, IL USA. [Schiller, Gary J.] Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. [Socie, Gerald] Hop St Louis, Paris, France. [Szer, Jeffrey] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RP Weisdorf, DJ (reprint author), Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. EM weisd001@umn.edu OI Szer, Jeff/0000-0001-6783-2301 FU National Cancer Institute (NCI) [24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation; Ariad; Be the Match Foundation; Blue Cross; Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from the NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. NR 32 TC 15 Z9 15 U1 0 U2 10 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD FEB PY 2013 VL 98 IS 2 BP 185 EP 192 DI 10.3324/haematol.2012.062059 PG 8 WC Hematology SC Hematology GA 096PD UT WOS:000315415800010 PM 22983587 ER PT J AU Chen, WJ Sun, CC Chen, SZ Meynard, D Babitt, JL Lin, HY AF Chen, Wenjie Sun, Chia Chi Chen, Shanzhuo Meynard, Delphine Babitt, Jodie L. Lin, Herbert Y. TI A novel validated enzyme-linked immunosorbent assay to quantify soluble hemojuvelin in mouse serum SO HAEMATOLOGICA LA English DT Article ID IRON-REGULATORY PROTEIN; HEPCIDIN EXPRESSION; JUVENILE HEMOCHROMATOSIS; PEPTIDE HEPCIDIN; DOWN-REGULATION; HOMEOSTASIS; OVERLOAD; ANEMIA; TMPRSS6; BMP6 AB Hemojuvelin is a critical regulator of hepcidin expression and can be cleaved by proteases to form soluble hemojuvelin. Soluble hemojuvelin has been recently identified in human serum but the presence and quantity of soluble hemojuvelin in mouse serum is unknown. We developed a two-site enzyme-linked immunosorbent assay using a monoclonal anti-hemojuvelin as the capture antibody and a biotinylated polyclonal anti-hemojuvelin as the detection antibody to quantify the levels of soluble hemojuvelin in mouse serum. We validated this assay using cell-conditioned media and serum from Hemojuvelin-null and Bone morphogenetic protein 6-null mice. We also used this validated assay to measure serum soluble hemojuvelin concentrations in mice receiving an acute low iron or high iron treatment. This two-site enzyme-linked immunosorbent assay was highly specific for mouse hemojuvelin, with a lower limit of detection at 13.2-26.8 ng/mL of soluble hemojuvelin in mouse serum. The median serum soluble hemojuvelin concentration in wild-type C57BL/6J mice was 57.9+/-22 ng/mL, which is 4- to 20-fold less than that reported in healthy human volunteers. After acute low iron diet treatment in these mice, serum soluble hemojuvelin levels were increased and correlated with lowered serum iron levels and decreased hepatic hepcidin expression. An acute high iron diet in wild-type mice or chronically iron-overloaded Bone morphogenetic protein 6-null mice did not significantly lower serum soluble hemojuvelin concentrations. Here we report reliable quantitation of mouse serum soluble hemojuvelin using a novel and validated enzyme-linked immunosorbent assay. This assay may provide a useful tool to elucidate the source and physiological role of serum soluble hemojuvelin in hepcidin regulation and iron metabolism using well-established mouse models of iron-related disorders. C1 [Chen, Wenjie; Sun, Chia Chi; Chen, Shanzhuo; Meynard, Delphine; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol,Sch Med, Boston, MA 02115 USA. RP Lin, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol,Sch Med, Boston, MA 02115 USA. EM Lin.Herbert@mgh.harvard.edu RI meynard, delphine/B-4236-2014 FU Cooley's Anemia Foundation; NRSA [T32-DK7540-27]; NIH [RO1-DK087727, RO1 DK-069533, RO1 DK-071837]; Massachusetts General Hospital FX This work was supported by a Cooley's Anemia Foundation Research Fellowship (to WC), by a NRSA grant T32-DK7540-27 (to CCS), by a NIH grant RO1-DK087727 and a Claflin Distinguished Scholar Award from the Massachusetts General Hospital (to JLB), and by NIH grants RO1 DK-069533 and RO1 DK-071837 (to HYL). NR 42 TC 9 Z9 10 U1 1 U2 9 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD FEB PY 2013 VL 98 IS 2 BP 296 EP 304 DI 10.3324/haematol.2012.070136 PG 9 WC Hematology SC Hematology GA 096PD UT WOS:000315415800025 PM 22875629 ER PT J AU Chinitz, JS Chen, D Goyal, P Wilson, S Islam, F Nguyen, T Wang, Y Hurtado-Rua, S Simprini, L Cham, M Levine, RA Devereux, RB Weinsaft, JW AF Chinitz, Jason S. Chen, Debbie Goyal, Parag Wilson, Sean Islam, Fahmida Thanh Nguyen Wang, Yi Hurtado-Rua, Sandra Simprini, Lauren Cham, Matthew Levine, Robert A. Devereux, Richard B. Weinsaft, Jonathan W. TI Mitral Apparatus Assessment by Delayed Enhancement CMR Relative Impact of Infarct Distribution on Mitral Regurgitation SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE mitral regurgitation; myocardial infarction; papillary muscle infarction ID ACUTE MYOCARDIAL-INFARCTION; PAPILLARY-MUSCLE DYSFUNCTION; QUANTITATIVE DOPPLER ASSESSMENT; CARDIAC MAGNETIC-RESONANCE; VALVULAR REGURGITATION; CLINICAL-SIGNIFICANCE; CONTRAST-ENHANCEMENT; IRREVERSIBLE INJURY; ATRIAL-FIBRILLATION; VALVE AB OBJECTIVES This study sought to assess patterns and functional consequences of mitral apparatus infarction after acute myocardial infarction (AMI). BACKGROUND The mitral apparatus contains 2 myocardial components: papillary muscles and the adjacent left ventricular (LV) wall. Delayed-enhancement cardiac magnetic resonance (DE-CMR) enables in vivo study of inter-relationships and potential contributions of LV wall and papillary muscle infarction (PMI) to mitral regurgitation (MR). METHODS Multimodality imaging was performed: CMR was used to assess mitral geometry and infarct pattern, including 3D DE-CMR for PMI. Echocardiography was used to measure MR. Imaging occurred 27 +/- 8 days after AMI (CMR, echocardiography within 1 day). RESULTS A total of 153 patients with first AMI were studied; PMI was present in 30% (n = 46 [72% posteromedial, 39% anterolateral]). When stratified by angiographic culprit vessel, PMI occurred in 65% of patients with left circumflex, 48% with right coronary, and only 14% of patients with left anterior descending infarctions (p <0.001). Patients with PMI had more advanced remodeling as measured by LV size and mitral annular diameter (p <0.05). Increased extent of PMI was accompanied by a stepwise increase in mean infarct transmurality within regional LV segments underlying each papillary muscle (p <0.001). Prevalence of lateral wall infarction was 3-fold higher among patients with PMI compared to patients without PMI (65% vs. 22%, p <0.001). Infarct distribution also impacted MR, with greater MR among patients with lateral wall infarction (p = 0.002). Conversely, MR severity did not differ on the basis of presence (p = 0.19) or extent (p = 0.12) of PMI, or by angiographic culprit vessel. In multivariable analysis, lateral wall infarct size (odds ratio 1.20/% LV myocardium [95% confidence interval: 1.05 to 1.39], p = 0.01) was independently associated with substantial (moderate or greater) MR even after controlling for mitral annular (odds ratio 1.22/mm [1.04 to 1.43], p = 0.01), and LV end-diastolic diameter (odds ratio 1.11/mm [0.99 to 1.23], p = 0.056). CONCLUSIONS Papillary muscle infarction is common after AMI, affecting nearly one-third of patients. Extent of PMI parallels adjacent LV wall injury, with lateral infarction-rather than PMI-associated with increased severity of post-AMI MR. (J Am Coll Cardiol Img 2013;6:220-34) (C) 2013 by the American College of Cardiology Foundation C1 [Chinitz, Jason S.; Chen, Debbie; Goyal, Parag; Wilson, Sean; Islam, Fahmida; Devereux, Richard B.; Weinsaft, Jonathan W.] Weill Cornell Med Coll, Greenberg Cardiol Div, Dept Med, New York, NY 10021 USA. [Thanh Nguyen; Wang, Yi; Weinsaft, Jonathan W.] Weill Cornell Med Coll, Dept Radiol, New York, NY 10021 USA. [Hurtado-Rua, Sandra] Weill Cornell Med Coll, Dept Biostat, New York, NY 10021 USA. [Simprini, Lauren] Mem Sloan Kettering Canc Ctr, Div Cardiol, New York, NY 10021 USA. [Cham, Matthew] Mt Sinai Med Ctr, New York, NY 10029 USA. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Weinsaft, JW (reprint author), Weill Cornell Med Coll, Starr 4,525 East 68th St, New York, NY 10021 USA. EM jww2001@med.cornell.edu FU Lantheus Medical Imaging; Doris Duke Clinical Scientist Development Award [K23 HL102249-01] FX This work was supported by Lantheus Medical Imaging, and a Doris Duke Clinical Scientist Development Award (K23 HL102249-01) to Dr. Weinsaft. The authors have reported they have no relationships relevant to the contents of this paper to disclose. NR 47 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD FEB PY 2013 VL 6 IS 2 BP 220 EP 234 DI 10.1016/j.jcmg.2012.08.016 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 097XX UT WOS:000315507900011 PM 23489536 ER PT J AU Jin, JO Han, XZ Yu, Q AF Jin, Jun-O Han, Xiaozhe Yu, Qing TI Interleukin-6 induces the generation of IL-10-producing Tr1 cells and suppresses autoimmune tissue inflammation SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Interleukin-6; Interleukin-10; Tr1 cells; Autoimmune disease; Immune-regulatory; Inflammation ID REGULATORY T-CELLS; ARYL-HYDROCARBON RECEPTOR; C-MAF; IL-10 PRODUCTION; TH17 CELLS; EXPRESSION; DIFFERENTIATION; IL-27; RESPONSES; EFFECTOR AB Compared with its pro-inflammatory function, the mechanisms underlying the anti-inflammatory effect of IL-6 are poorly understood. IL-6 can cooperate with TGF-beta to induce IL-10 production in Th17 cells in vitro. However, the effect of IL-6 on generation of Tr1 cells and the in vivo importance of this effect are mostly uncharacterized. In this study, we showed that in vitro, IL-6 can induce the generation of IL-10-producing Tr1 cells from naive CD4 T cells, independently of IL-27 and TGF-beta. IL-6 induces IL-21 production in CD4 T cells and IL-10-inducing effect of IL-6 requires both IL-21 and IL-2. Although IL-6 cannot induce IL-10 production in CD8 T cells in a cell-autonomous manner, it can do so indirectly through promoting CD4 T cell IL-21 production. The IL-10-producing T cells induced by IL-6 have phenotypic, genetic and functional traits of Tr1 cells and can suppress LPS-induced in vivo inflammatory response in an IL-10-dependent fashion. Blockade of IL-6 in two autoimmune inflammation models, induced respectively by anti-CD3 antibody or Treg-depletion, led to reduction in IL-10-producing T cells and exacerbated inflammation of lung and intestine. Thus, we delineated critical pathways involved in IL-6-induced generation of Tr1 cells and demonstrated the importance of this event in restraining autoimmune tissue inflammation. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Jin, Jun-O; Han, Xiaozhe; Yu, Qing] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. RP Yu, Q (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA. EM qyu@forsyth.org FU National Institutes of Health [P30DE020751] FX We thank Drs. T. Kawai, DJ. Smith and MA. Taubman for advice and support in this project; Drs. K. Shortman and A. Lew for critical reading of the manuscript; and Dr. M. Kajiya and Z. Li and for technical assistance. This entire study was supported by the National Institutes of Health (P30DE020751). NR 43 TC 34 Z9 37 U1 1 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 2013 VL 40 BP 28 EP 44 DI 10.1016/j.jaut.2012.07.009 PG 17 WC Immunology SC Immunology GA 095XJ UT WOS:000315368000004 PM 22921334 ER PT J AU Jeon, HJ Bae, J Woo, JM AF Jeon, Hong Jin Bae, Joomi Woo, Jong-Min TI Recent statistics and risk factors of suicide in children and adolescents SO JOURNAL OF THE KOREAN MEDICAL ASSOCIATION LA Korean DT Article DE Adolescent; Suicide; Risk factors ID PROTECTIVE FACTORS; SELF-HARM; ASSOCIATION; DEPRESSION; SAMPLE; YOUTH AB Youth suicide is like the tip of an iceberg; while many adolescents have died from suicide, many more adolescents have been harmed by suicide attempts and self-injury. Suicide influences not only the victims, but also their family members, friends, teachers, and neighbors. Witnesses can suffer from posttraumatic stress disorder. Suicide is the second leading cause of death among adolescents worldwide and the first cause of death among Korean adolescents. The number of suicides in Korea, especially among high school students and female students, is rapidly increasing when compared with Western countries. Suicide accounted for 28.2% of deaths among Korean adolescents in 2010. There were 4.44% and 18.97% of adolescents who had attempted suicide and had experienced suicidal ideation in their lifetime, which shows that many adolescents have a potential risk for suicide. Previous studies in Western countries have revealed that risk factors for adolescent suicide consist of three categories: sociodemographic factors (male and low socioeconomic and educational status), mental health factors (depression and drug abuse), and individual negative life events and family diversity (family history of suicidal behavior, parental death, and child abuse). In conclusion, suicide is common and rapidly increasing in Korean adolescents. However, the risk factors of suicide and suicide behaviors in Korean adolescents are yet to be determined. A well-designed nationwide survey is needed to investigate the prevalence and risk factors of suicide behaviors and mental disorders among Korean adolescents. C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depress Ctr,Dept Psychiat, Seoul, South Korea. [Jeon, Hong Jin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02115 USA. [Bae, Joomi] Korea Youth Counselling & Welf Inst, Seoul, South Korea. [Woo, Jong-Min] Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. [Woo, Jong-Min] Inje Univ, Stress Res Inst, Seoul, South Korea. [Woo, Jong-Min] Natl Evidence Based Healthcare Collaborating Agcy, Seoul, South Korea. RP Woo, JM (reprint author), Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. EM jongmin.woo@gmail.com FU National Evidence-based Healthcare Collaborating Agency [NM11-003] FX This study was fully funded by the National Evidence-based Healthcare Collaborating Agency (NM11-003). NR 25 TC 4 Z9 4 U1 5 U2 40 PU KOREAN MEDICAL ASSOC PI SEOUL PA 302-75 INCHON-1 DONG, YONGSAN-GU, SEOUL, 140-721, SOUTH KOREA SN 1975-8456 J9 J KOREAN MED ASSOC JI J. Korean Med. Assoc. PD FEB PY 2013 VL 56 IS 2 BP 93 EP 99 DI 10.5124/jkma.2013.56.2.93 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 098NC UT WOS:000315555000003 ER PT J AU Meimarakis, G Angele, M Conrad, C Schauer, R Weidenhagen, R Crispin, A Giessen, C Preissler, G Wiedemann, M Jauch, KW Heinemann, V Stintzing, S Hatz, RA Winter, H AF Meimarakis, Georgios Angele, Martin Conrad, Claudius Schauer, Rolf Weidenhagen, Rolf Crispin, Alexander Giessen, Clemens Preissler, Gerhard Wiedemann, Max Jauch, Karl-Walter Heinemann, Volker Stintzing, Sebastian Hatz, Rudolf A. Winter, Hauke TI Combined resection of colorectal hepatic-pulmonary metastases shows improved outcome over chemotherapy alone SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Article DE Colorectal cancer; Prognostic factors; Pulmonary metastases; Liver metastases; Surgical resection; Survival ID SURGICAL-TREATMENT; PLUS OXALIPLATIN; COLON-CANCER; FINAL REPORT; PHASE-III; CARCINOMA; FLUOROURACIL; SURVIVAL; LEUCOVORIN; RECURRENCE AB The objective of this retrospective study was to assess the survival of patients after resection of hepatic and pulmonary colorectal metastases to identify predictors of long-term survival. Patients receiving chemotherapy alone were compared to patients receiving surgery and chemotherapy in a matched-pair analysis with the following criteria: UICC stage, grading, and date of initial primary tumor occurrence. A total of 30 patients with liver and lung metastases of colorectal carcinoma underwent resection. In 20 cases, complete resection was achieved (median survival, 67 months). Incomplete resection and preoperatively elevated carcinoembryonic antigen (CEA) levels are independent risk factors for reduced survival. Patients developing pulmonary metastases prior to hepatic metastases had the worst prognosis. Surgical resection significantly increased survival compared to chemotherapy alone in matched-pair analysis (65 vs. 30 months, p = 0.03). Incomplete resection and elevated CEA levels are predictors of poor outcome. Matched-paired analysis confirmed that surgical resection in combination with chemotherapy appears to be superior to chemotherapy alone. C1 [Meimarakis, Georgios; Angele, Martin; Weidenhagen, Rolf; Preissler, Gerhard; Jauch, Karl-Walter; Hatz, Rudolf A.; Winter, Hauke] Univ Munich Grosshadern, Dept Gen Thorac Surg, D-81377 Munich, Germany. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schauer, Rolf] Traunstein Hosp, Dept Surg, Traunstein, Germany. [Crispin, Alexander; Wiedemann, Max] Univ Munich, Dept Med Informat Biometry & Epidemiol, Munich, Germany. [Giessen, Clemens; Heinemann, Volker; Stintzing, Sebastian] Univ Munich Grosshadern, Dept Oncol, D-81377 Munich, Germany. [Giessen, Clemens; Heinemann, Volker; Stintzing, Sebastian] Univ Munich Grosshadern, Ctr Comprehens Canc, D-81377 Munich, Germany. RP Winter, H (reprint author), Univ Munich Grosshadern, Dept Gen Thorac Surg, Marchioninistr 15, D-81377 Munich, Germany. EM hauke.winter@med.uni-muenchen.de RI Winter, Hauke/I-1394-2013; OI Winter, Hauke/0000-0001-8911-6218; Stintzing, Sebastian /0000-0002-3297-5801 FU Chiles Foundation, Portland, OR FX This work was supported by a grant from the Chiles Foundation, Portland, OR. The Chiles Foundation is a nonprofit research institution supporting biomedical research. The Chiles Foundation had no influence on the design or conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation, review, or approval of the manuscript. NR 27 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD FEB PY 2013 VL 398 IS 2 BP 265 EP 276 DI 10.1007/s00423-012-1046-1 PG 12 WC Surgery SC Surgery GA 089GX UT WOS:000314900100010 PM 23314791 ER PT J AU Brown, JR Kim, HT Armand, P Cutler, C Fisher, DC Ho, V Koreth, J Ritz, J Wu, C Antin, JH Soiffer, RJ Gribben, JG Alyea, EP AF Brown, J. R. Kim, H. T. Armand, P. Cutler, C. Fisher, D. C. Ho, V. Koreth, J. Ritz, J. Wu, C. Antin, J. H. Soiffer, R. J. Gribben, J. G. Alyea, E. P. TI Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome SO LEUKEMIA LA English DT Article DE CLL; RIC; myeloablative; SCT; prognostic model ID BONE-MARROW-TRANSPLANTATION; PROGRESSION-FREE SURVIVAL; VERSUS-HOST-DISEASE; POOR-PROGNOSIS; MATCHED ANALYSIS; INITIAL THERAPY; FLUDARABINE; RITUXIMAB; CYCLOPHOSPHAMIDE; TRIAL AB Chronic lymphocytic leukemia (CLL) remains incurable with chemoimmunotherapy, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential for cure. We assessed the outcomes of 108 CLL patients undergoing first allogeneic HSCTs, 76 with reduced-intensity (RIC) and 32 with myeloablative conditioning (MAC) between 1998 and 2009 at Dana-Farber Cancer Institute. With median follow-up of 5.9 years in surviving patients, the 5-year overall survival (OS) for the entire cohort is 63% for RIC regimens and 49% for MAC regimens (P=0.18). The risk of death declined significantly starting in 2004, and we found that 5-year OS for HSCT between 2004 and 2009 was 83% for RIC regimens compared with 47% for MAC regimens (P=0.003). For RIC transplantation, we developed a prognostic model based on predictors of progression-free survival (PFS), specifically remission status, lactate dehydrogenase, comorbidity score and lymphocyte count, and found 5-year PFS to be 83% for Score 0, 63% for Score 1, 24% for Score 2 and 6% for Score >= 3 (P<0.0001). We conclude that RIC HSCT for CLL in the current era is associated with excellent long-term PFS and OS, and, as potentially curative therapy, should be considered early in the disease course of relapsed high-risk CLL patients. Leukemia (2013) 27, 362-369; doi:10.1038/leu.2012.228 C1 [Brown, J. R.; Kim, H. T.; Armand, P.; Cutler, C.; Fisher, D. C.; Ho, V.; Koreth, J.; Ritz, J.; Wu, C.; Antin, J. H.; Soiffer, R. J.; Gribben, J. G.; Alyea, E. P.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Brown, J. R.; Armand, P.; Cutler, C.; Fisher, D. C.; Ho, V.; Koreth, J.; Ritz, J.; Wu, C.; Antin, J. H.; Soiffer, R. J.; Gribben, J. G.; Alyea, E. P.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Brown, J. R.; Armand, P.; Cutler, C.; Fisher, D. C.; Ho, V.; Koreth, J.; Ritz, J.; Wu, C.; Antin, J. H.; Soiffer, R. J.; Gribben, J. G.; Alyea, E. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jbrown2@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [K23 CA115682-01, PO1 HL070149, PO1 CA81538, A129530, P01 CA142106]; Jock and Bunny Adams Research and Education Endowment; Ted and Eileen Pasquarello Research Fund FX We are indebted to the nurses, medical oncology fellows, house staff and social workers of the Dana-Farber Cancer Institute and Brigham and Women's Hospital for their excellent care of these patients. We thank the staff of the Connell-O'Reilly Cell Manipulation Laboratory and the Blood Component Laboratory of the Dana-Farber Cancer Institute for processing stem cells for these patients, and the data management staff for their tireless work in maintaining the DFCI BMT clinical data repository, without which this project would not be possible. This work was supported by NIH Grants K23 CA115682-01 to JRB, PO1 HL070149, PO1 CA81538 to JGG, A129530 to FLIS, P01 CA142106 to JHA, and by the Jock and Bunny Adams Research and Education Endowment and the Ted and Eileen Pasquarello Research Fund. JRB is a Scholar of the American Society of Hematology as well as a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 38 TC 44 Z9 44 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2013 VL 27 IS 2 BP 362 EP 369 DI 10.1038/leu.2012.228 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 098MO UT WOS:000315553600013 PM 22955330 ER PT J AU Magrangeas, F Avet-Loiseau, H Gouraud, W Lode, L Decaux, O Godmer, P Garderet, L Voillat, L Facon, T Stoppa, AM Marit, G Hulin, C Casassus, P Tiab, M Voog, E Randriamalala, E Anderson, KC Moreau, P Munshi, NC Minvielle, S AF Magrangeas, F. Avet-Loiseau, H. Gouraud, W. Lode, L. Decaux, O. Godmer, P. Garderet, L. Voillat, L. Facon, T. Stoppa, A. M. Marit, G. Hulin, C. Casassus, P. Tiab, M. Voog, E. Randriamalala, E. Anderson, K. C. Moreau, P. Munshi, N. C. Minvielle, S. TI Minor clone provides a reservoir for relapse in multiple myeloma SO LEUKEMIA LA English DT Article DE multiple myeloma; genomic analysis; nonlinear evolution ID STEM-CELL TRANSPLANTATION; LYMPHOBLASTIC-LEUKEMIA; COPY-NUMBER; EVOLUTION; ABNORMALITIES; THALIDOMIDE; DYSCRASIAS; PREDNISONE; MECHANISMS; MELPHALAN AB Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-kappa B-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission. Leukemia (2013) 27, 473-481; doi:10.1038/leu.2012.226 C1 [Magrangeas, F.; Gouraud, W.; Decaux, O.; Moreau, P.; Minvielle, S.] Univ Nantes, CNRS, INSERM, UMR 892,UMR 6299, F-44007 Nantes 01, France. [Magrangeas, F.; Avet-Loiseau, H.; Lode, L.; Moreau, P.; Minvielle, S.] CHU Nantes, F-44007 Nantes 01, France. [Gouraud, W.] Inst Cancerol Ouest, Nantes, France. [Decaux, O.] Ctr Hosp Univ, Rennes, France. [Godmer, P.] Ctr Hosp, Vannes, France. [Garderet, L.] Hop St Antoine, F-75571 Paris, France. [Voillat, L.] Ctr Hosp, Chalon Sur Saone, France. [Facon, T.] CHU Lille, F-59037 Lille, France. [Stoppa, A. M.] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Marit, G.] Ctr Hosp Univ, Bordeaux, France. [Hulin, C.] Ctr Hosp Univ, Nancy, France. [Casassus, P.] Hop Avicenne, F-93009 Bobigny, France. [Tiab, M.] Ctr Hosp, La Roche Sur Yon, France. [Voog, E.] Ctr Jean Bernard, Le Mans, France. [Randriamalala, E.] Ctr Hosp Mileterie, Poitiers, France. [Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Harvard Med Sch, Leebow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Harvard Med Sch, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Munshi, N. C.] Boston VA Healthcare Syst, Boston, MA USA. RP Minvielle, S (reprint author), Univ Nantes, CNRS, INSERM, UMR 892,UMR 6299, 8 Quai Moncousu BP 70721, F-44007 Nantes 01, France. EM stephane.minvielle@inserm.fr RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015; Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 OI FACON, THIERRY/0000-0001-7705-8460; FU IFM; French National Research Agency [R08079NS]; French Institute National du Cancer [R09076NN]; National Institutes of Health [PO1 CA155258-01, RO1-124929, P50-100007, PO1-78378]; Department of Veterans Affairs Merit Review Awards FX This study was supported by IFM; the French National Research Agency, Grant R08079NS (to SM); the French Institute National du Cancer, Grant R09076NN (to HA-L); the National Institutes of Health, Grants PO1 CA155258-01 (to NCM, SM, HA-L and KCA), RO1-124929 (to NCM), P50-100007 and PO1-78378 (to NCM and KCA), and Department of Veterans Affairs Merit Review Awards. We thank Elise Douillard, Magali Devic, Emilie Maurenton and Nathalie Roi for excellent technical expertise. We also thank Marie C Bene for critical reading of the manuscript NR 33 TC 42 Z9 44 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2013 VL 27 IS 2 BP 473 EP 481 DI 10.1038/leu.2012.226 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 098MO UT WOS:000315553600025 PM 22874878 ER PT J AU Mata, IF Alvarez, V Ribacoba, R Infante, J Sierra, M Gomez-Garre, P Mir, P Waldherr, S Yearout, D Zabetian, CP AF Mata, Ignacio F. Alvarez, Victoria Ribacoba, Renee Infante, Jon Sierra, Maria Gomez-Garre, Pilar Mir, Pablo Waldherr, Sarah Yearout, Dora Zabetian, Cyrus P. CA Latin Amer Res Consortium Genetics TI Novel Lrrk2-p.S1761R mutation is not a common cause of Parkinson's disease in Spain SO MOVEMENT DISORDERS LA English DT Letter C1 [Mata, Ignacio F.; Waldherr, Sarah; Yearout, Dora; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Alvarez, Victoria] Hosp Univ Cent Asturias, Lab Genet Mol, Inst Invest Nefrol, Oviedo, Spain. [Ribacoba, Renee] Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain. [Infante, Jon; Gomez-Garre, Pilar; Mir, Pablo] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain. [Infante, Jon; Sierra, Maria] Marques de Valdecilla Univ Hosp, Dept Neurol, Santander, Spain. [Gomez-Garre, Pilar; Mir, Pablo] Univ Seville, Hosp Univ Virgen del Rocio, Unidad Trastornos Movimiento, CSIC,Serv Neurol & Neurofisiol Clin,Inst Biomed S, Seville, Spain. RP Mata, IF (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM nachofm@u.washington.edu RI IBIS, MOVIMIENTO/P-3309-2015; Mir, Pablo/C-8662-2013; OI Mir, Pablo/0000-0003-1656-302X; Fernandez Mata, Ignacio/0000-0003-1198-0633; Gomez-Garre, Pilar/0000-0002-0437-6182; Zabetian, Cyrus/0000-0002-7739-4306 FU BLRD VA [I01 BX000531]; FIC NIH HHS [R25 TW009345]; NINDS NIH HHS [P50 NS062684, R01 NS065070] NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB PY 2013 VL 28 IS 2 BP 248 EP 248 DI 10.1002/mds.25293 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096JF UT WOS:000315399300026 PM 23389884 ER PT J AU Cai, XM Han, S Feske, SK Chou, SHY AF Cai, Xuemei Han, Steve Feske, Steven K. Chou, Sherry H. -Y. TI Pearls and Oy-sters: Small but consequential Intracerebral hemorrhage caused by lenticulostriate artery aneurysm SO NEUROLOGY LA English DT Editorial Material ID SUBARACHNOID HEMORRHAGE; ANGIOGRAPHY C1 [Cai, Xuemei; Feske, Steven K.; Chou, Sherry H. -Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Cai, Xuemei; Han, Steve] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cai, Xuemei; Han, Steve; Feske, Steven K.; Chou, Sherry H. -Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Cai, XM (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM xcai@partners.org RI Chou, Sherry/G-5779-2015 FU NINDS NIH HHS [K23 NS073806] NR 10 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 9 BP E89 EP E91 DI 10.1212/WNL.0b013e31828406a2 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 097CI UT WOS:000315451200002 PM 23439707 ER PT J AU Joseph, J Loscalzo, J AF Joseph, Jacob Loscalzo, Joseph TI Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype SO NUTRIENTS LA English DT Review DE selenium; cardiovascular disease; redox balance; methylation; epigenesis; gene expression; heart failure; fibrosis; methionine; homocysteine ID CHRONIC HEART-FAILURE; ABERRANT CRYPT FORMATION; DIETARY SELENIUM; DNA METHYLATION; VITAMIN-E; COXSACKIEVIRUS B3; SERUM SELENIUM; DEFICIENT MICE; GLUTATHIONE-PEROXIDASE; MYOCARDIAL-INFARCTION AB Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease. C1 [Joseph, Jacob] VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. [Joseph, Jacob; Loscalzo, Joseph] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Loscalzo, J (reprint author), VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. EM Jacob.joseph@va.gov; jloscalzo@partners.org FU National Institutes of Health [HL89734, HL061795, HL107192, HL070819, HL048743, HL108630] FX This work presented in this article was supported by the National Institutes of Health grant number HL89734 (J.J.), and National Institutes of Health grant numbers HL061795, HL107192, HL070819, HL048743, and HL108630 (J.L.). NR 96 TC 17 Z9 17 U1 0 U2 27 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD FEB PY 2013 VL 5 IS 2 BP 340 EP 358 DI 10.3390/nu5020340 PG 19 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 096JW UT WOS:000315401100002 PM 23434902 ER PT J AU Harden, RN Oaklander, AL Burton, AW Perez, RSGM Richardson, K Swan, M Barthel, J Costa, B Graciosa, JR Bruehl, S AF Harden, R. Norman Oaklander, Ann Louise Burton, Allen W. Perez, Roberto S. G. M. Richardson, Kathryn Swan, Melanie Barthel, Jennifer Costa, Brienne Graciosa, Joseph R. Bruehl, Stephen TI Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 4th Edition SO PAIN MEDICINE LA English DT Review DE Complex Regional Pain Syndrome; Reflex Sympathetic Dystrophy; Guidelines; Diagnosis; Therapy ID REFLEX SYMPATHETIC DYSTROPHY; SYNDROME TYPE-I; SPINAL-CORD STIMULATION; RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; CONCENTRATION CAPSAICIN PATCH; DOUBLE-BLIND CROSSOVER; FACILITATED NEUROGENIC INFLAMMATION; RECEPTOR ANTAGONIST AMANTADINE; CHRONIC POSTHERPETIC NEURALGIA AB Objective This is the fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy). Methods Expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included. The literature review was supplemented with knowledge gained from extensive empirical clinical experience, particularly in areas where high-quality evidence to guide therapy is lacking. Results The research quality, clinical relevance, and state of the art of diagnostic criteria or treatment modalities are discussed, sometimes in considerable detail with an eye to the expert practitioner in each therapeutic area. Levels of evidence are mentioned when available, so that the practitioner can better assess and analyze the modality under discussion, and if desired, to personally consider the citations. Tables provide details on characteristics of studies in different subject domains described in the literature. Conclusions In the humanitarian spirit of making the most of all current thinking in the area, balanced by a careful case-by-case analysis of the risk/cost vs benefit analysis, the authors offer these practical guidelines. C1 [Harden, R. Norman; Graciosa, Joseph R.] Rehabil Inst Chicago, Ctr Pain Studies, Chicago, IL 60611 USA. [Richardson, Kathryn] Rehabil Inst Chicago, Ctr Pain Management, Chicago, IL 60611 USA. [Barthel, Jennifer] Rehabil Inst Chicago, Vocat Rehabil Serv, Chicago, IL 60611 USA. [Harden, R. Norman] Northwestern Univ, Dept Phys Med, Chicago, IL 60611 USA. [Harden, R. Norman] Northwestern Univ, Dept Rehabil, Chicago, IL 60611 USA. [Harden, R. Norman] Northwestern Univ, Chicago, IL 60611 USA. [Oaklander, Ann Louise] Massachusetts Gen Hosp, Dept Neurol & Pathol, Boston, MA 02114 USA. [Oaklander, Ann Louise] Harvard Univ, Sch Med, Boston, MA USA. [Burton, Allen W.] Houston Pain Associates PLLC, Houston, TX USA. [Swan, Melanie] Ohio State Univ, Wexner Med Ctr, Inpatient Rehabil Serv, Acquired Brain Injury Team, Columbus, OH 43210 USA. [Costa, Brienne] Snoqualmie Valley Hosp, Rehabil Dept, Snoqualmie, WA USA. [Bruehl, Stephen] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Perez, Roberto S. G. M.] Vrije Univ Amsterdam, Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands. RP Harden, RN (reprint author), Rehabil Inst Chicago, Ctr Pain Studies, 345 E Super St, Chicago, IL 60611 USA. EM nharden@ric.org FU Reflex Sympathetic Dystrophy Syndrome Association (RSDSA); Dutch Alliance for Improvement of Paincare (DALI); Pfizer; Board of the Reflex Sympathetic Dystrophy Syndrome Association FX This work was sponsored by the Reflex Sympathetic Dystrophy Syndrome Association (RSDSA), on which Dr. Harden currently serves as the Chairman of the Research Committee and is on the Board of Directors. Dr. Bruehl serves on the RSDSA Scientific Advisory Board. Dr. Burton consults for Medtronic, Inc. and Boston Scientific. Dr. Perez has received consultancy fees and an unrestricted research grant from the Dutch Alliance for Improvement of Paincare (DALI), which is funded by Pfizer. All other authors have no conflicts of interest to disclose.; The authors would like to extend their gratitude to James Broatch and the Board of the Reflex Sympathetic Dystrophy Syndrome Association for their sponsorship, guidance, and continued support of this project. NR 343 TC 87 Z9 92 U1 3 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD FEB PY 2013 VL 14 IS 2 BP 180 EP 229 DI 10.1111/pme.12033 PG 50 WC Medicine, General & Internal SC General & Internal Medicine GA 099TL UT WOS:000315644800002 PM 23331950 ER PT J AU Schneider, JC Gerrard, P Goldstein, R Divita, MA Niewczyk, P Ryan, CM Kowalske, K Zafonte, R AF Schneider, Jeffrey C. Gerrard, Paul Goldstein, Richard Divita, Margaret A. Niewczyk, Paulette Ryan, Colleen M. Kowalske, Karen Zafonte, Ross TI The Impact of Comorbidities and Complications on Burn Injury Inpatient Rehabilitation Outcomes SO PM&R LA English DT Article ID SPINAL-CORD-INJURY; TRAUMATIC BRAIN-INJURY; LENGTH-OF-STAY; STROKE REHABILITATION; RISK-FACTORS; ADMINISTRATIVE DATABASES; ACUTE-CARE; MEDICAL REHABILITATION; ADULT PATIENTS; MORTALITY AB Objective: To examine the impact of comorbidities and complications on burn inpatient rehabilitation facilities (IRE) outcomes. Design: A retrospective cross-sectional study. Setting: Inpatient rehabilitation hospitals. Patients: A total of 4572 patients with a primary diagnosis of burn injury from the Uniform Data System for Medical Rehabilitation database from 2002 to 2010. Methods or Interventions: Regression analyses were used to determine whether 3 different comorbidity measures (Charlson Comorbidity Index, Elixhauser Comoribidity Index, Centers for Medicare and Medicaid Services Comorbidity Tiers) and 1 complication measure improved the predictive model (c-statistic) for each outcome measure. Main Outcome Measurements: Community discharge, Functional Independence Measure (FIM) gain, length of stay efficiency, transfer to acute care within the first 3 days of IRE stay, and transfer to acute care for all time periods. Results: For all outcomes, there was no difference between the Standard Model and the models that include the comorbidity and complication variables as measured by the c-statistic confidence intervals. Conclusions: Comorbidities and complications did not significantly affect burn IRE outcomes. Future research is needed to examine the impact of comorbidities and complications on outcomes of other IRE populations to better understand the implications for current and future health care policy. PM R2013;5:114-121 C1 [Schneider, Jeffrey C.; Gerrard, Paul; Goldstein, Richard; Zafonte, Ross] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Divita, Margaret A.; Niewczyk, Paulette] Uniform Data Syst Med Rehabilitat, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Ryan, Colleen M.] Shriners Hosp Children Boston, Dept Surg, Boston, MA USA. [Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA 02114 USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. EM jcschneider@partners.org OI Gerrard, Paul/0000-0003-0654-5354; DiVita, Margaret/0000-0002-4878-2959 FU Department of Defense FX grant, Department of Defense NR 46 TC 11 Z9 11 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD FEB PY 2013 VL 5 IS 2 BP 114 EP 121 DI 10.1016/j.pmrj.2012.07.014 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 095VP UT WOS:000315363400005 PM 22981003 ER PT J AU Murray, AL Morgenroth, DC Czerniecki, JM AF Murray, Andrew L. Morgenroth, David C. Czerniecki, Joseph M. TI Residual Limb Claudication in a Traumatic Transtibial Amputee SO PM&R LA English DT Article ID BACK-PAIN; PHANTOM PAIN; AMPUTATION AB Residual limb pain is a common symptom in the lower extremity amputee population with a fairly broad differential diagnosis. One etiology of residual limb pain that has previously received limited discussion in the literature is that of vascular claudication. Increased awareness of this etiology is important given the prevalence of vascular disease in both the general population and in lower extremity amputees. This article discusses a presentation of residual limb vascular claudication, describes a clinical approach to the problem, and discusses a potential pathophysiologic mechanism for vascular claudication in the amputee that differs from the nonamputee. PM R 2013;5:152-154 C1 [Murray, Andrew L.; Morgenroth, David C.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Morgenroth, David C.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. RP Morgenroth, DC (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, 1660 S Columbian Way,RCS 117, Seattle, WA 98108 USA. EM dmorgen@uw.edu OI Morgenroth, David/0000-0002-0226-7775 NR 15 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD FEB PY 2013 VL 5 IS 2 BP 152 EP 154 DI 10.1016/j.pmrj.2012.08.003 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 095VP UT WOS:000315363400011 PM 23415251 ER PT J AU Mishra, RK Li, YM Ricardo, AC Yang, W Keane, M Cuevas, M Christenson, R DeFilippi, C Chen, J He, J Kallem, RR Raj, DS Schelling, JR Wright, J Go, AS Shlipak, MG AF Mishra, Rakesh K. Li, Yongmei Ricardo, Ana C. Yang, Wei Keane, Martin Cuevas, Magdalena Christenson, Robert DeFilippi, Christopher Chen, Jing He, Jiang Kallem, Radhakrishna R. Raj, Dominic S. Schelling, Jeffrey R. Wright, Jackson Go, Alan S. Shlipak, Michael G. CA Chronic Renal Insufficiency Cohort TI Association of N-Terminal Pro-B-Type Natriuretic Peptide With Left Ventricular Structure and Function in Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort [CRIC]) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; CARDIOVASCULAR EVENTS; DIASTOLIC FUNCTION; MORTALITY; BNP; HEMODIALYSIS; HYPERTROPHY; MASS; CKD; ECHOCARDIOGRAPHY AB We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants' predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants' likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13-0.15; p < 0.001) and LV systolic dysfunction (net reclassification improvement 0.28, 95% CI 0.27 to 0.30; p < 0.001) but not diastolic dysfunction (net reclassification improvement 0.10, 95% CI 0.10 to 0.11; p = 0.07). In conclusion, in this large chronic kidney disease cohort without heart failure, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:432-438) C1 [Mishra, Rakesh K.; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mishra, Rakesh K.; Li, Yongmei; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ricardo, Ana C.] Univ Illinois, Chicago, IL USA. [Yang, Wei] Univ Penn, Sci & Data Coordinating Ctr, Philadelphia, PA 19104 USA. [Keane, Martin; Cuevas, Magdalena] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Christenson, Robert; DeFilippi, Christopher] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Chen, Jing; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Kallem, Radhakrishna R.] Univ Penn, Philadelphia, PA 19104 USA. [Raj, Dominic S.] George Washington Univ, Washington, DC USA. [Schelling, Jeffrey R.] MetroHlth Med Ctr, Cleveland, OH USA. [Schelling, Jeffrey R.; Wright, Jackson] Case Western Univ, Cleveland, OH USA. [Go, Alan S.] Kaiser Permanente Div Res, Oakland, CA USA. RP Mishra, RK (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM rakesh.mishra@ucsf.edu RI Yang, Wei/A-9223-2009 OI Yang, Wei/0000-0001-8984-4389 FU Chronic Renal Insufficiency Cohort General Clinical Research Center and Clinical and Translational Science Award [UL1 RR-024134, UL1 RR-025005, M01RR-16500, UL1 RR-024989, M01 RR-000042, UL1 RR-024986, UL1 RR-029879, 2 U01 DK060902]; [R01 DK066488] FX This project was supported by R01 DK066488 award (to principal investigator M. G. Shlipak); and in part by the Chronic Renal Insufficiency Cohort General Clinical Research Center and Clinical and Translational Science Award grants: UL1 RR-024134 to the University of Pennsylvania (Philadelphia, Pennsylvania), UL1 RR-025005 to Johns Hopkins University (Baltimore, Maryland), M01RR-16500 to University of Maryland (College Park, Maryland), UL1 RR-024989 to Case Western Reserve University (Cleveland, Ohio), M01 RR-000042 and UL1 RR-024986 to University of Michigan (Ann Arbor, Michigan), UL1 RR-029879 to University of Illinois at Chicago (Chicago, Illinois), and 2 U01 DK060902 to the Kaiser Permanente Division of Research in Oakland (Oakland, California). NR 28 TC 16 Z9 18 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2013 VL 111 IS 3 BP 432 EP 438 DI 10.1016/j.amjcard.2012.10.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 083BM UT WOS:000314437700022 PM 23178053 ER PT J AU Yo, K Yu, YM Zhao, GZ Bonab, AA Aikawa, N Tompkins, RG Fischman, AJ AF Yo, Kikuo Yu, Yong-Ming Zhao, Gaofeng Bonab, Ali A. Aikawa, Naoki Tompkins, Ronald G. Fischman, Alan J. TI Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE brown adipose tissue; burn injury-induced hypermetabolism; mitochondria dysfunction ID HUMAN SKELETAL-MUSCLE; ADULT HUMANS; NONSHIVERING THERMOGENESIS; UNCOUPLING PROTEINS; ANTIOXIDANT PEPTIDE; ENERGY-EXPENDITURE; REPERFUSION INJURY; OBESITY; STRESS; UCP1 AB Yo K, Yu YM, Zhao G, Bonab AA, Aikawa N, Tompkins RG, Fischman AJ. Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism. Am J Physiol Endocrinol Metab 304: E331-E341, 2013. First published November 20, 2012; doi:10.1152/ajpendo.00098.2012.-Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1. C1 [Yo, Kikuo; Yu, Yong-Ming; Zhao, Gaofeng; Bonab, Ali A.; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA 02114 USA. [Yo, Kikuo; Yu, Yong-Ming; Zhao, Gaofeng; Bonab, Ali A.; Tompkins, Ronald G.; Fischman, Alan J.] Massachusetts Gen Hosp, Burn Unit, Boston, MA 02114 USA. [Yo, Kikuo; Yu, Yong-Ming; Zhao, Gaofeng; Bonab, Ali A.; Tompkins, Ronald G.; Fischman, Alan J.] Harvard Univ, Sch Med, Boston, MA USA. [Aikawa, Naoki] Keio Univ, Sch Med, Dept Emergency & Crit Care Med, Tokyo, Japan. RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM aajjff@gmail.com FU National Institutes of Health [2P50 GM-21700-27A, P30 DK-004056]; Shriners Hospitals for Children [84050]; Morningside Technology Advisory, Inc. FX This study was supported in part by grants from the National Institutes of Health (2P50 GM-21700-27A, P30 DK-004056), Shriners Hospitals for Children (no. 84050), and Morningside Technology Advisory, Inc. NR 47 TC 6 Z9 7 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 2013 VL 304 IS 4 BP E331 EP E341 DI 10.1152/ajpendo.00098.2012 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 092SI UT WOS:000315141900001 PM 23169784 ER PT J AU Shao, RX Zhang, LL Hong, Z Goto, K Cheng, D Chen, WC Jilg, N Kumthip, K Fusco, DN Peng, LF Chung, RT AF Shao, Run-Xuan Zhang, Leiliang Hong, Zhi Goto, Kaku Cheng, Du Chen, Wen-Chi Jilg, Nikolaus Kumthip, Kattareeya Fusco, Dahlene N. Peng, Lee F. Chung, Raymond T. TI SOCS1 abrogates IFN's antiviral effect on hepatitis C virus replication SO ANTIVIRAL RESEARCH LA English DT Article DE Hepatitis C virus; SOCS1; Interferon; ISG; JFH1 ID JAK-STAT PATHWAY; INTERFERON-ALPHA; RIBAVIRIN; CYTOKINE; ACTIVATION; SUPPRESSOR; EXPRESSION; INHIBITOR; INFECTION; PROTEINS AB Suppressor of cytokine signaling 1 (SOCS1) and suppressor of cytokine signaling 3 (SOCS3) have been thought to block type I interferon (IFN) signaling. We have previously reported that SOCS3 suppresses HCV replication in an mTOR-dependent manner. However, the relationship between SOCS1 and HCV replication remains unclear. Here, we found that overexpression of SOCS1 alone did not have an effect on HCV RNA replication. However, suppression of HCV replication by IFN-alpha, was rescued by SOCS1 overexpression. The upregulation of HCV replication by SOCS1 overexpression in the presence of IFN is likely a result of the impairment of IFN signaling by SOCS1 and subsequent induction of ISGs. Knockdown of SOCS1 alone with specific shRNA enhanced the antiviral effect of IFN compared with negative control. Thus, SOCS1 acts as a suppressor of type I IFN function against HCV. (C) 2012 Elsevier B.V. All rights reserved. C1 [Zhang, Leiliang; Hong, Zhi] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China. [Zhang, Leiliang; Hong, Zhi] Peking Union Med Coll, Beijing 100730, Peoples R China. [Shao, Run-Xuan; Zhang, Leiliang; Goto, Kaku; Cheng, Du; Chen, Wen-Chi; Jilg, Nikolaus; Kumthip, Kattareeya; Fusco, Dahlene N.; Peng, Lee F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [AI069939, AI082630, DK078772]; Intramural Research Program of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences [2012IPB101] FX This work was supported by Grants AI069939, AI082630 and DK078772 (R.T.C.) from the National Institutes of Health, 2012IPB101 from Intramural Research Program of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences (to L.Z.). We thank Drs. Nobuyuki Kato and Masanori Ikeda for the gift of OR6 cells; Dr. Francis Chisari for the Huh7.5.1 cell line; Dr. Takaji Wakita for the infectious HCV virus JFH1 DNA construct; Dr. Christoph J. Auernhammer for pCR3.1/SOCS1 construct. NR 27 TC 7 Z9 7 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2013 VL 97 IS 2 BP 101 EP 107 DI 10.1016/j.antiviral.2012.12.001 PG 7 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 095FG UT WOS:000315319500003 PM 23237992 ER PT J AU Lee, J AF Lee, Jongsoon TI Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 Diabetes SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE Adipose tissue macrophage (ATM); Insulin resistance; Obesity; Inflammation ID DIET-INDUCED OBESITY; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; FACTOR-KAPPA-B; INDUCED HEPATIC STEATOSIS; FREE FATTY-ACIDS; SKELETAL-MUSCLE; IKK-BETA; SYSTEMIC INFLAMMATION; 3T3-L1 ADIPOCYTES AB It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and type 2 Diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in type 2 Diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of type 2 Diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesity-induced inflammation and the roles ATMs play in this process. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lee, J (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM jongsoon.lee@joslin.harvard.edu FU American Diabetes Association [RA 110BS97]; Boston Obesity Nutrition Research Center (NIDDK) [DK046200]; NIH/NIDDK [DK80380] FX The author was supported by grants from the American Diabetes Association (RA 110BS97), Pilot and Feasibility awards from the Boston Obesity Nutrition Research Center (DK046200, NIDDK) and NIH/NIDDK (DK80380). NR 143 TC 36 Z9 41 U1 3 U2 51 PU PHARMACEUTICAL SOC KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD FEB PY 2013 VL 36 IS 2 BP 208 EP 222 DI 10.1007/s12272-013-0023-8 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 093BZ UT WOS:000315168000009 PM 23397293 ER PT J AU Mikuls, TR Padala, PR Sayles, HR Yu, F Michaud, K Caplan, L Kerr, GS Reimold, A Cannon, GW Richards, JS Lazaro, D Thiele, GM Boscarino, JA AF Mikuls, Ted R. Padala, Prasad R. Sayles, Harlan R. Yu, Fang Michaud, Kaleb Caplan, Liron Kerr, Gail S. Reimold, Andreas Cannon, Grant W. Richards, J. Steuart Lazaro, Deana Thiele, Geoffrey M. Boscarino, Joseph A. TI Prospective study of posttraumatic stress disorder and disease activity outcomes in US veterans with rheumatoid arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID GULF-WAR VETERANS; CHRONIC PAIN; ANXIETY DISORDERS; VIETNAM VETERANS; PTSD SYMPTOMS; CARE; ASSOCIATION; MORTALITY; EXPOSURE; ILLNESS AB Objective To examine the relationship between posttraumatic stress disorder (PTSD) and disease activity in US veterans with rheumatoid arthritis (RA). Methods US veterans with RA were enrolled in a longitudinal observational study and were categorized as having PTSD, other anxiety/depression disorders, or neither of these psychiatric diagnoses using administrative codes. Generalized linear mixed-effects models were used to examine the associations of the diagnostic groups with outcomes measured over a mean followup period of 3.0 years. Results At enrollment, 1,522 patients had a mean age of 63 years, they were primarily men (91%), and a majority (78%) reported white race. A diagnosis of PTSD was observed in 178 patients (11.7%), and other anxiety/depression diagnoses (excluding PTSD) were found in 360 patients (23.7%). The presence of a PTSD diagnosis was independently associated with higher values of self-reported pain, physical impairment, tender joint count, and worse patient global well-being scores compared to patients with no psychiatric diagnosis. There were no significant group differences in swollen joint count, erythrocyte sedimentation rate, or Disease Activity Score in 28 joints. There were no differences between any outcomes comparing those with PTSD and those with other anxiety/depression diagnoses. Conclusion In this RA cohort, the diagnosis of PTSD was associated with worse patient-reported outcomes and tender joint counts, but not with other physician- or laboratory-based measures of disease activity. These results suggest that PTSD, along with other anxiety/depression disorders, may affect RA disease activity assessments that rely on patient-reported outcomes and the resulting treatment decisions. C1 [Mikuls, Ted R.; Thiele, Geoffrey M.] Omaha VAMC, Omaha, NE 68198 USA. [Mikuls, Ted R.; Sayles, Harlan R.; Yu, Fang; Michaud, Kaleb; Thiele, Geoffrey M.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Padala, Prasad R.] Little Rock VAMC, Little Rock, AR USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. [Caplan, Liron] Univ Colorado, Sch Med, Denver, CO USA. [Kerr, Gail S.; Richards, J. Steuart] DC VAMC, Washington, DC USA. [Kerr, Gail S.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Reimold, Andreas] Dallas VAMC, Dallas, TX USA. [Reimold, Andreas] Univ Texas SW, Dallas, TX USA. [Cannon, Grant W.] George E Wahlen VAMC, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Lazaro, Deana] Brooklyn VAMC, Brooklyn, NY USA. [Boscarino, Joseph A.] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. RP Mikuls, TR (reprint author), Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. EM tmikuls@unmc.edu RI Yu, Fang/B-9874-2013; OI Thiele, Geoffrey/0000-0001-5688-8596 FU Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; Veterans Health Administration; Abbott Laboratories; Bristol-Myers Squibb; Veterans Affairs Health Services Research and Development Program Career Development Award [CDA 07-221] FX Supported by the Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center. The Veterans Affairs Rheumatoid Arthritis registry is supported by the Veterans Affairs Health Services Research and Development Program of the Veterans Health Administration and unrestricted research grants from Abbott Laboratories and Bristol-Myers Squibb. Dr. Mikuls' work was supported by the Veterans Health Administration (Veterans Affairs Merit award). Dr. Caplan's work was supported by a Veterans Affairs Health Services Research and Development Program Career Development Award (CDA 07-221). NR 36 TC 9 Z9 9 U1 4 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2013 VL 65 IS 2 BP 227 EP 234 DI 10.1002/acr.21778 PG 8 WC Rheumatology SC Rheumatology GA 083LW UT WOS:000314466600008 PM 22740431 ER PT J AU Fryer, SL Jorgensen, KW Yetter, EJ Daurignac, EC Watson, TD Shanbhag, H Krystal, JH Mathalon, DH AF Fryer, Susanna L. Jorgensen, Kasper W. Yetter, Elizabeth J. Daurignac, Elsa C. Watson, Todd D. Shanbhag, Harshad Krystal, John H. Mathalon, Daniel H. TI Differential brain response to alcohol cue distractors across stages of alcohol dependence SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Abstinence; Alcoholism; Amygdala; Anterior cingulate; Cognitive control; Distraction; Inferior parietal lobule ID ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; ABSTINENT ALCOHOLICS; VENTRAL STRIATUM; ODDBALL TASK; ACTIVATION; FMRI; AMYGDALA; STIMULI; EMOTION AB Altered attention to alcohol-related cues is implicated in the craving and relapse cycle characteristic of alcohol dependence (ALC). Prior cue reactivity studies typically invoke explicit attention to alcohol cues, so the neural response underlying incidental cue exposure remains unclear. Here, we embed infrequent, task-irrelevant alcohol and non-alcohol cues in an attention-demanding task, enabling evaluation of brain responses to distracting alcohol cues. Alcohol dependent individuals, across illness phase (n = 44), and controls (n = 20) performed a cue-reactivity fMRI target detection task. Significant Group-by-Distractor effects were observed in dorsal anterior cingulate cortex (ACC), inferior parietal lobule, and amygdala. Controls and long-term abstainers increased recruitment of attention and cognitive control regions, while recent and long-term abstainers decreased limbic recruitment to alcohol distractors. Across phases of ALC, self-reported craving positively correlated with cue-related activations in ventral ACC, medial prefrontal cortex, and cerebellum. Results indicate that brain responses elicited by incidental alcohol cues differentiate phases of ALC. (C) 2012 Elsevier B.V. All rights reserved. C1 [Fryer, Susanna L.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Fryer, Susanna L.; Jorgensen, Kasper W.; Yetter, Elizabeth J.; Shanbhag, Harshad; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Daurignac, Elsa C.] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. [Watson, Todd D.] Lewis & Clark Coll, Dept Psychol, Portland, OR 97219 USA. [Krystal, John H.; Mathalon, Daniel H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU NIAAA [P50-AA-12870]; Alcohol Beverage Medical Research Foundation; NIMH [T32 MH089920] FX This work was supported by grants from NIAAA P50-AA-12870 (to J.H. Krystal), the Alcohol Beverage Medical Research Foundation (to D.H. Mathalon), and NIMH T32 MH089920 (to J.M. Ford). The authors thank Drs. Mark George and Andreas Heinz for facilitating access to stimulus sets developed in their laboratories. NR 63 TC 10 Z9 10 U1 7 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD FEB PY 2013 VL 92 IS 2 BP 282 EP 291 DI 10.1016/j.biopsycho.2012.10.004 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 095DU UT WOS:000315315700025 PM 23131612 ER PT J AU Micallef, IN Jacobsen, ED Shaughnessy, P Gandhi, PJ Calandra, G van Rhee, F Uberti, J AF Micallef, I. N. Jacobsen, E. D. Shaughnessy, P. Gandhi, P. J. Calandra, G. van Rhee, F. Uberti, J. TI G-CSF plus plerixafor (Mozobil) to mobilize hematopoietic stem cells in patients with thrombocytopenia or leukopenia prior to auto-SCT SO BONE MARROW TRANSPLANTATION LA English DT Letter ID NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; AMD3100 C1 [Micallef, I. N.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA. [Jacobsen, E. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shaughnessy, P.] Texas Transplant Inst, San Antonio, TX USA. [Gandhi, P. J.; Calandra, G.] Sanofi Oncol, Cambridge, MA USA. [van Rhee, F.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Uberti, J.] Karmanos Canc Inst, Detroit, MI USA. RP Micallef, IN (reprint author), Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA. EM micallef.ivana@mayo.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2013 VL 48 IS 2 BP 303 EP 304 DI 10.1038/bmt.2012.125 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 094BY UT WOS:000315239200029 PM 22773123 ER PT J AU Uchida, Y Raina, D Kharbanda, S Kufe, D AF Uchida, Yasumitsu Raina, Deepak Kharbanda, Surender Kufe, Donald TI Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the treatment of breast cancer cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE MUC1; GO-203; doxorubicin; taxol; synergy; breast cancer ID TRANSCRIPTION FACTOR; APOPTOTIC RESPONSE; SURVIVAL RESPONSE; ACTIVATION; PROTEIN; STRESS; GENE AB Mucin 1 (MUC1) is a heterodimeric glycoprotein that is aberrantly overexpressed in most human breast cancers. The oncogenic MUC1-C subunit promotes survival and blocks the apoptotic response to genotoxic anticancer agents. In the present studies, human MCF-7 and ZR-75-1 breast cancer cells were treated with the MUC1-C inhibitor, GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization and thereby its oncogenic function. Treatment with GO-203 was found to promote the apoptotic response of MCF-7 and ZR-75-1 cells to the therapeutic drugs taxol and doxorubicin (DOX). This effect was (1) attenuated by a pan-caspase inhibitor and (2) mediated, at least in part, by activation of the effector caspase-7 and cleavage of the downstream substrate PARP. Further analysis of the interaction between GO-203 and taxol using isobolograms, which evaluate the nature of the interaction of two drugs, demonstrated that the combination is highly synergistic. These results were supported by combination index (CI) analysis with values of less than 1. GO-203 was also highly synergistic with DOX in studies of both MCF-7 and ZR-75-1 breast cancer cells. These findings indicate that blocking MUC1-C function could be effective in combination with taxol and DOX for the treatment of breast cancer. C1 [Uchida, Yasumitsu; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Raina, Deepak; Kharbanda, Surender] Genus Oncol, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Donald_Kufe@dfci.harvard.edu FU National Cancer Institute of the National Institutes of Health [CA97098, CA166480] FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers CA97098 and CA166480. NR 26 TC 10 Z9 10 U1 0 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2013 VL 14 IS 2 BP 127 EP 134 DI 10.4161/cbt.22634 PG 8 WC Oncology SC Oncology GA 083MP UT WOS:000314468700009 PM 23114713 ER PT J AU Lee, HJ Schaefer, G Heffron, TP Shao, L Ye, XF Sideris, S Malek, S Chan, E Merchant, M La, H Ubhayakar, S Yauch, RL Pirazzoli, V Politi, K Settleman, J AF Lee, Ho-June Schaefer, Gabriele Heffron, Timothy P. Shao, Lily Ye, Xiaofen Sideris, Steve Malek, Shiva Chan, Emily Merchant, Mark La, Hank Ubhayakar, Savita Yauch, Robert L. Pirazzoli, Valentina Politi, Katerina Settleman, Jeff TI Noncovalent Wild-type-Sparing Inhibitors of EGFR T790M SO CANCER DISCOVERY LA English DT Article ID TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; ACUTE MYELOID-LEUKEMIA; ACQUIRED-RESISTANCE; INCREASED SENSITIVITY; POTENT INHIBITOR; FLT3 INHIBITORS; GEFITINIB; RECEPTOR; PKC412 AB Approximately half of EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with small-molecule EGFR kinase inhibitors develop drug resistance associated with the EGF receptor (EGFR) T790M "gatekeeper" substitution, prompting efforts to develop covalent EGFR inhibitors, which can effectively suppress EGFR T790M in preclinical models. However, these inhibitors have yet to prove clinically efficacious, and their toxicity in skin, reflecting activity against wild-type EGFR, may limit dosing required to effectively suppress EGFR T790M in vivo. While profiling sensitivity to various kinase inhibitors across a large cancer cell line panel, we identified indolocarbazole compounds, including a clinically well-tolerated FLT3 inhibitor, as potent and reversible inhibitors of EGFR T790M that spare wild-type EGFR. These findings show the use of broad cancer cell profiling of kinase inhibitor efficacy to identify unanticipated novel applications, and they identify indolocarbazole compounds as potentially effective EGFR inhibitors in the context of T790M-mediated drug resistance in NSCLC. SIGNIFICANCE: EGFR-mutant lung cancer patients who respond to currently used EGFR kinase inhibitors invariably develop drug resistance, which is associated with the EGFR T790M resistance mutation in about half these cases. We unexpectedly identified a class of reversible potent inhibitors of EGFR T790M that do not inhibit wild-type EGFR, revealing a promising therapeutic strategy to overcome T790M-associated drug-resistant lung cancers. Cancer Discov; 3(2); 168-81. (C) 2012 AACR. See related commentary by Brewer and Pao, p. 138. C1 [Lee, Ho-June; Ye, Xiaofen; Yauch, Robert L.; Settleman, Jeff] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA. [Schaefer, Gabriele; Shao, Lily] Genentech Inc, Dept Res Oncol, San Francisco, CA 94080 USA. [Heffron, Timothy P.] Genentech Inc, Dept Discovery Chem, San Francisco, CA 94080 USA. [Sideris, Steve; Malek, Shiva] Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA. [Chan, Emily; Merchant, Mark] Genentech Inc, Dept Canc Signaling & Translat Oncol, San Francisco, CA 94080 USA. [La, Hank; Ubhayakar, Savita] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA. [Lee, Ho-June; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Politi, Katerina] Yale Univ, Sch Med, New Haven, CT USA. RP Settleman, J (reprint author), Genentech Inc, Discovery Oncol, 1 DNA Way, San Francisco, CA 94080 USA. EM settleman.jeffrey@gene.com RI Lee, Ho-June/D-8855-2014; OI Lee, Ho-June/0000-0002-7019-2533; Merchant, Mark/0000-0003-0690-8581 FU National Institutes of Health [R00CA131488, R01CA120247]; Uniting Against Lung Cancer; Labrecque Foundation; American Italian Cancer Foundation FX This study was supported by grants R00CA131488 and R01CA120247 from the National Institutes of Health (to K. Politi). Additional support was received from Uniting Against Lung Cancer (to K. Politi), the Labrecque Foundation (to K. Politi), and the American Italian Cancer Foundation (to V. Pirazzoli). NR 39 TC 40 Z9 40 U1 2 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD FEB PY 2013 VL 3 IS 2 BP 168 EP 181 DI 10.1158/2159-8290.CD-12-0357 PG 14 WC Oncology SC Oncology GA 088IA UT WOS:000314826300023 PM 23229345 ER PT J AU Theodos, G Raymond, C Becker, MC Thornton, J Ellis, SG Bhatt, DL Raymond, RE AF Theodos, Gus Raymond, Chad Becker, Matthew C. Thornton, Julie Ellis, Stephen G. Bhatt, Deepak L. Raymond, Russell E. TI Arteriotomy closure device safety after percutaneous coronary intervention in the direct thrombin inhibitor era: A comparative study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bivalirudin; angio-seal; perclose; manual compression ID CARDIAC-CATHETERIZATION; VASCULAR COMPLICATIONS; RANDOMIZED-TRIAL; MANUAL COMPRESSION; MYOCARDIAL-INFARCTION; HEART-ASSOCIATION; CLINICAL-TRIALS; FEMORAL-ARTERY; ANGIO-SEAL; REGISTRY AB Objectives To investigate the safety and risk of vascular complications of arteriotomy closure devices (ACD) with the direct thrombin inhibitor bivalirudin in patients undergoing percutaneous coronary intervention (PCI). Background ACDs and manual compression have been shown to have a similar risk of complications in the setting of PCI with heparin +/- glycoprotein (GP) IIb/IIIa inhibitor usage. In many centers bivalirudin is becoming the most frequent type of anticoagulation used during PCI. We sought to determine the risk of vascular complications using Angio-Seal, Perclose, and manual compression for groin hemostasis using predominantly bivalirudin. Methods Our institution's interventional database retrospectively identified 14,354 consecutive patients undergoing PCI from 2000 to 2008. Patients were grouped by the adjunctive anticoagulation used (bivalirudin vs. heparin + GP IIb/IIIa inhibitors) as well as ACD employed. The incidence of complications was evaluated using multivariable analysis to account for baseline differences between groups. Results Patients undergoing PCI with adjunctive bivalirudin had significantly fewer complications overall, regardless of closure method (2.9% vs. 8.7%, P < 0.001). The Perclose group had significantly fewer complications than the Angio-Seal and manual compression groups (3.9% vs. 5.6% vs. 9.0%, P < 0.001) respectively; the Angio-Seal group had significantly fewer complications than manual compression. Multivariable analysis also identified age 65, female gender, BMI 26, and operator as independent predictors of complications. Conclusions The use of adjunctive bivalirudin during PCI was associated with fewer vascular complications. In addition, the Perclose and Angio-Seal devices had significantly fewer complications than manual compression and women 65 are at highest risk. (c) 2012 Wiley Periodicals, Inc. C1 [Theodos, Gus; Raymond, Chad; Thornton, Julie; Ellis, Stephen G.; Raymond, Russell E.] Cleveland Clin, Cleveland, OH 44106 USA. [Becker, Matthew C.] St Vincent Heart & Vasc Ctr, Erie, PA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Raymond, RE (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave,J2-03, Cleveland, OH 44195 USA. EM raymonr@ccf.org NR 29 TC 4 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2013 VL 81 IS 2 BP 294 EP 300 DI 10.1002/ccd.24393 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 093UO UT WOS:000315218400015 PM 22826017 ER PT J AU Jama, A Schainfeld, RM AF Jama, Abdi Schainfeld, Robert M. TI Filling the void: "She's Got Gaps, I've Got Gaps. Together, We Fill Gaps." Rocky Balboa (1976) SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID POSTCATHETERIZATION PSEUDOANEURYSMS; INJECTION C1 [Jama, Abdi; Schainfeld, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sect Vasc Med,Div Cardiol, Boston, MA USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM rschainfeld@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2013 VL 81 IS 2 BP 308 EP 309 DI 10.1002/ccd.24787 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 093UO UT WOS:000315218400018 PM 23423925 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Pushing the boundaries of renal denervation for resistant hypertension SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID TRIAL C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02132 USA. RP Bhatt, DL (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2013 VL 81 IS 2 BP 340 EP 341 DI 10.1002/ccd.24785 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 093UO UT WOS:000315218400024 PM 23423926 ER PT J AU Fox, ER Musani, SK Barbalic, M Lin, HH Yu, B Ogunyankin, KO Smith, NL Kutlar, A Glazer, NL Post, WS Paltoo, DN Dries, DL Farlow, DN Duarte, CW Kardia, SL Meyers, KJ Sun, YV Arnett, DK Patki, AA Sha, J Cui, XQ Samdarshi, TE Penman, AD Bibbins-Domingo, K Buzkova, P Benjamin, EJ Bluemke, DA Morrison, AC Heiss, G Carr, JJ Tracy, RP Mosley, TH Taylor, HA Psaty, BM Heckbert, SR Cappola, TP Vasan, RS AF Fox, Ervin R. Musani, Solomon K. Barbalic, Maja Lin, Honghuang Yu, Bing Ogunyankin, Kofo O. Smith, Nicholas L. Kutlar, Abdullah Glazer, Nicole L. Post, Wendy S. Paltoo, Dina N. Dries, Daniel L. Farlow, Deborah N. Duarte, Christine W. Kardia, Sharon L. Meyers, Kristin J. Sun, Yan V. Arnett, Donna K. Patki, Amit A. Sha, Jin Cui, Xiangqui Samdarshi, Tandaw E. Penman, Alan D. Bibbins-Domingo, Kirsten Buzkova, Petra Benjamin, Emelia J. Bluemke, David A. Morrison, Alanna C. Heiss, Gerardo Carr, J. Jeffrey Tracy, Russell P. Mosley, Thomas H. Taylor, Herman A. Psaty, Bruce M. Heckbert, Susan R. Cappola, Thomas P. Vasan, Ramachandran S. TI Genome-Wide Association Study of Cardiac Structure and Systolic Function in African Americans The Candidate Gene Association Resource (CARe) Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE echocardiography; ethnic; genome-wide association studies; left atrium genetics; left ventricular mass genetics ID LEFT-VENTRICULAR MASS; COMMON DISEASES; HYPERTROPHY; VARIANTS; SUSCEPTIBILITY; CONTRACTILITY; HYPERTENSION; HYPERGEN; LINKAGE; MARKERS AB Background-Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study. Methods and Results-Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genome-wide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0x10(-7)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43x10(-7)) for left ventricular mass, rs7213314 in WIPI1 (P=1.68x10(-7)) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57x10(-8)) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02x10(-7)) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN. Conclusions-In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes. (Circ Cardiovasc Genet. 2013;6:37-46.) C1 [Fox, Ervin R.; Musani, Solomon K.; Yu, Bing; Samdarshi, Tandaw E.; Penman, Alan D.; Mosley, Thomas H.; Taylor, Herman A.] Univ Mississippi, Sch Med, Dept Med, Jackson, MS 39216 USA. [Barbalic, Maja; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Lin, Honghuang; Glazer, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Ogunyankin, Kofo O.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98195 USA. [Smith, Nicholas L.] US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Grp Hlth Res Inst,Grp Hlth Cooperat, Seattle, WA USA. [Kutlar, Abdullah] Georgia Hlth Sci Univ, Dept Med, Augusta, GA USA. [Post, Wendy S.] Johns Hopkins Sch Med, Dept Med, Div Cardiol, Baltimore, MD USA. [Paltoo, Dina N.] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dries, Daniel L.] Yale Univ, Sch Med, Dept Med, Div Cardiovasc, New Haven, CT 06510 USA. [Farlow, Deborah N.] Broad Inst Massachusetts Inst Technol & Harvard U, Boston, MA USA. [Duarte, Christine W.; Patki, Amit A.; Cui, Xiangqui] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Arnett, Donna K.; Sha, Jin] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Kardia, Sharon L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Meyers, Kristin J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. [Sun, Yan V.] Emory Univ, Sch Med, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA USA. [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Carr, J. Jeffrey] Wake Forest Univ, Sch Med Publ Hlth & Translat Sci, Salem, NC USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT 05405 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Carr, J. Jeffrey] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Fox, ER (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 North State St, Jackson, MS 39216 USA. EM efox@medicine.umsmed.edu RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; Lin, Honghuang/0000-0003-3043-3942; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health (NIH)/National Institute on Minority Health and Health Disparities (NIMHD) [P20]; Novartis; Celgene Corp; Global Iron Summit; NIH [HL 100245, R01 HL09257, RC1 HD101056, R01 HL102214, R01 AG028321]; Candidate Gene Association Resource Study, Exome Sequencing Project; ARIC, NIH; NIH; National Heart, Lung, and Blood Institute [HL 087652]; University of North Carolina at Chapel Hill [N01-HC-55015]; Baylor Medical College [N01-HC-55016]; University of Mississippi Medical Center [N01-HC-55021]; University of Minnesota [N01-HC-55019, N01-HC-48048]; Johns Hopkins University [N01-HC-55020, N01-HC-85081, N01 HC-15103]; University of Texas, Houston [N01-HC-55017]; University of North Carolina, Forsyth County [N01-HC-55018]; University of Washington [N01-HC-85079, N01 HC-55222, U01 HL080295, N01-HC-95159]; Wake Forest University [N01-HC-85080, N01-HC-45205]; University of Pittsburgh [N01-HC-85082]; University of California, Davis [N01-HC-85083]; University of California, Irvine [N01-HC-85084, N01-HC-45134, N01-HC-95100]; New England Medical Center [N01-HC-85085]; University of Vermont [N01-HC-85086]; Georgetown University [N01-HC-35129]; University of Wisconsin [N01-HC-75150]; Geisinger Clinic [N01-HC-45133]; Case Western Reserve University [RO1 HL46380-01-16]; University of Illinois [N01-HB-72982, N01-HB-97062]; Howard University [N01-HB-72991, N01-HB-97061]; University of Miami [N01-HB-72992, N01-HB-97064]; Duke University [N01-HB-72993]; George Washington University [N01-HB-72994]; University of Tennessee [N01-HB-72995, N01-HB-97070]; Yale University [N01-HB-72996, N01-HB-97072]; Children's Hospital-Philadelphia [N01-HB-72997, N01-HB-97056]; University of Chicago [N01-HB-72998, N01-HB-97053]; Medical College of Georgia [N01-HB-73000, N01-HB-97060]; Washington University [N01-HB-73001, N01-HB-97071]; Jewish Hospital and Medical Center of Brooklyn [N01-HB-73002]; Trustees of Health and Hospitals of the City of Boston, Inc. [N01-HB-73003]; Children's Hospital-Oakland [N01-HB-73004, N01-HB-97054]; University of Mississippi [N01-HB-73005, N01-HC-95171]; St. Luke's Hospital-New York [N01-HB-73006]; Alta Bates-Herrick Hospital [N01-HB-97051]; Columbia University [N01-HB-97058]; St. Jude's Children's Research Hospital [N01-HB-97066]; Research Foundation, State University of New York-Albany [N01-HB-97068, N01-HB-97069]; New England Research Institute [N01-HB-97073]; Interfaith Medical Center-Brooklyn [N01-HB-97085]; University of Alabama at Birmingham [N01-HC-48047, N01-HC-95095]; Northwestern University [N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050]; Tufts-New England Medical Center [N01-HC-45204]; Harbor-UCLA Research and Education Institute [N01-HC-05187]; Boston University [N01-HC-25195]; Jackson State University [N01-HC-95170]; Tougaloo College [N01-HC-95172]; Regents of the University of California [N01-HC-95160]; [R01 HD067264]; [RC4 AG039029]; [R01 HL101161-01-A1]; [R01 DK077950-03]; [RC1 HL100185]; [P60 MD002249] FX Dr Kutlar received research grants from National Institutes of Health (NIH)/National Institute on Minority Health and Health Disparities (NIMHD)-P20, Novartis, Celgene Corp. (>=$10000), and Global Iron Summit (<$10000). Dr Paltoo has ownership interest in a 529 College Plan and a Thrift Saving Plan (>$10000). Dr Kardia received research grants from R01 HD067264, RC4 AG039029, R01 HL101161-01-A1, R01 DK077950-03, RC1 HL100185, and P60 MD002249 (>$10000). Dr Sun received research grants from NIH HL 100245, Genetics of Hypertension Risk Factors, and Sequela in African Americans (>$10000). Dr Benjamin received research grants from R01 HL09257, RC1 HD101056, R01 HL102214, and R01 AG028321 (all NIH grants >$10000). Dr Tracy received research grants from Candidate Gene Association Resource Study, Exome Sequencing Project (>$10000). Dr Mosley received research grants from ARIC, ARIC-Neurocognitive Study, Predictors of Coronary Artery Calcification in an African American Cohort, GWAS of Ischemic Brain Vascular Injury, ARIC PET Amyloid Imaging Study, the Intracranial Atherosclerosis Disease and Cognitive Impairment Study, Parkinson Disease and Olfactory Function in the ARIC Study, and Identify Epidemiological Risk Factors for Abdominal Aortic Aneurysm Study (all NIH grants >$10000). Dr Taylor received research grants for the Jackson Heart Study (NIH grant >$10000). Dr Psaty received NIH grants (<$10000); he serves on the Data and Safety Monitoring Board for a clinical trial for a device (Zoll Life Cor <$10000) and service on the Steering Committee for Yale Open Data Project (Medtronic <$10000). Dr Heckbert received research grants from HL 087652 Whole Genome Association Study in the Cardiovascular Health Study (National Heart, Lung, and Blood Institute >$10000). Dr Vasan received an NIH grant (>$10000). The other authors report no conflicts.; Atherosclerotic Risk in Communities: University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), and University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study: University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), and University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study: Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease: University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc. (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St.; Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), and Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults: University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), and University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study: Boston University (N01-HC-25195); Jackson Heart Study: Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), and Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis: University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), and Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study: Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), and Johns Hopkins University (U01 HL053937). NR 28 TC 15 Z9 15 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2013 VL 6 IS 1 BP 37 EP 46 DI 10.1161/CIRCGENETICS.111.962365 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 094YL UT WOS:000315301500008 PM 23275298 ER PT J AU Yu, B Barbalic, M Brautbar, A Nambi, V Hoogeveen, RC Tang, WH Mosley, TH Rotter, JI deFilippi, CR O'Donnell, CJ Kathiresan, S Rice, K Heckbert, SR Ballantyne, CM Psaty, BM Boerwinkle, E AF Yu, Bing Barbalic, Maja Brautbar, Ariel Nambi, Vijay Hoogeveen, Ron C. Tang, Weihong Mosley, Thomas H. Rotter, Jerome I. deFilippi, Christopher R. O'Donnell, Christopher J. Kathiresan, Sekar Rice, Ken Heckbert, Susan R. Ballantyne, Christie M. Psaty, Bruce M. Boerwinkle, Eric CA CARDIoGRAM Consortium TI Association of Genome-Wide Variation With Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks A Meta-Analysis From Atherosclerosis Risk in Communities and Cardiovascular Health Studies SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics; genome-wide association study; troponin ID CORONARY-ARTERY-DISEASE; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SARCOMERE PROTEIN GENES; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; ALPHA-TROPOMYOSIN; HEART-FAILURE; MUTATIONS; ASSAY; MORTALITY AB Background-High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels. Methods and Results-We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374; P=9.06x10(-9)) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73x10(-8)) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004). Conclusions-We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results. (Circ Cardiovasc Genet. 2013;6:82-88.) C1 [Yu, Bing; Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Deptartment Med, Houston, TX 77030 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Tang, Weihong] Univ Minnesota, Deptartment Epidemiol, Minneapolis, MN USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Div Geriatr, Jackson, MS 39216 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [deFilippi, Christopher R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] NIH, Framingham Heart Study, Bethesda, MD 20892 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Boerwinkle, E (reprint author), Univ Texas Sch Publ Hlth, Ctr Human Genet, 1200 Herman Pressler E-447, Houston, TX 77030 USA. EM Eric.Boerwinkle@uth.tmc.edu FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN2682011000 08C, HHSN268201100009C, HHSN268201100010C, HHSN2682 01100011C, HHSN268201100012C, R01HL087641, R01HL59 367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, UL1RR025005]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Center for Research Resources CTSI [UL 1RR033176]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Burroughs Wellcome Fund; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium; National Heart, Lung, and Blood Institute. [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL085251, HL087652, HL105756] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN2682011000 08C, HHSN268201100009C, HHSN268201100010C, HHSN2682 01100011C, and HHSN268201100012C), R01HL087641, R01HL59 367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health, and NIH Roadmap for Medical Research. This Cardiovascular Health Study research was supported by the National Heart, Lung, and Blood Institute contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133,; and National Heart, Lung, and Blood Institute grants HL080295, HL075366, HL085251, HL087652, and HL105756, with additional contributions from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center for Research Resources CTSI grant UL 1RR033176 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center and the Cedars-Sinai Board of Governors' Chair in Medical Genetics (to Dr Rotter).; We acknowledge the essential role of The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium in developing and supporting this article. CHARGE members include the ARIC, the CHS, Framingham Heart Study (FHS) and Rotterdam Study (RS), and Age, Gene/Environment Susceptibility. The authors also thank the staff and participants of the ARIC and CHS study for their important contributions. Dr Yu is supported in part by the Burroughs Wellcome Fund. NR 30 TC 8 Z9 8 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2013 VL 6 IS 1 BP 82 EP 88 DI 10.1161/CIRCGENETICS.112.963058 PG 7 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 094YL UT WOS:000315301500013 PM 23247143 ER PT J AU Baffy, G AF Baffy, Gyoergy TI Allostasis in Nonalcoholic Fatty Liver Disease: Implications for Risk Assessment SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Allostasis; Allostatic load; Outcomes; Risk prediction; Allostatic score; Nonalcoholic fatty liver disease; Hepatocellular carcinoma ID UNFOLDED PROTEIN RESPONSE; HEPATOCELLULAR-CARCINOMA; METABOLIC-SYNDROME; NONCIRRHOTIC LIVERS; INSULIN-RESISTANCE; STRESS; LIPOTOXICITY; OBESITY; LOAD; STEATOHEPATITIS AB Allostasis, a concept of anticipatory physiological regulation in response to external and internal challenges, was originally developed in the context of neuroendocrinology and behavioral medicine. Allostasis preserves function under changing conditions by abandoning physiological set points and developing new ones. Allostatic load refers to the aggregate effect of adaptation throughout life, and corresponds to the wear and tear associated with this process. In response to chronic stress, allostatic load may accumulate faster than expected if sustained activation of regulatory systems exceeds optimum operating ranges; this results in increased risk of disease. Used in a broader sense, the allostatic model of adaptive responses, trade-offs, feed-forward cycles, and collateral damage provides a framework for assessing the involvement of environmental-genetic interactions and co-morbidities in the course of chronic disease and developing a comprehensive score for personalized risk prediction. The utility of this approach is illustrated for nonalcoholic fatty liver disease, a prevalent condition with common and less common outcomes. C1 [Baffy, Gyoergy] VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA. [Baffy, Gyoergy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Baffy, Gyoergy] VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. RP Baffy, G (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA. EM gbaffy@partners.org NR 50 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2013 VL 58 IS 2 BP 302 EP 308 DI 10.1007/s10620-012-2344-8 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094UZ UT WOS:000315291100006 PM 22886595 ER PT J AU Hermos, JA Altincatal, A Weber, HC Grotzinger, K Smoot, KJ Cho, K Gagnon, DR Lawler, EV AF Hermos, John A. Altincatal, Arman Weber, H. Christian Grotzinger, Kelly Smoot, Kyle J. Cho, Kelly Gagnon, David R. Lawler, Elizabeth V. TI Thrombocytopenia and Bleeding in Veterans with Non-hepatitis C-related Chronic Liver Disease SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Chronic liver disease; Thrombocytopenia; Hemorrhage; Veterans ID CIRRHOSIS; ARTICLE; SURVIVAL; COHORT; PREVALENCE; DRINKING AB Thrombocytopenia in chronic liver disease (CLD) typically reflects disease severity and may indicate an increased risk for bleeding. To describe the longitudinal course of thrombocytopenia and risks for bleeding in veteran patients with non-hepatitis C-related CLD. We identified 2,349 patients with non-hepatitis C-related CLD from databases of the New England Veterans Healthcare System between 1999 and 2008. The cohort was stratified by baseline platelet counts of < 50,000, 50-100,000, > 100,000-150,000, and > 150,000/mu l. Primary outcomes were the incidence and hazard rates for bleeding episodes requiring hospitalization and incident severe thrombocytopenia (< 50,000/mu l). Over a median follow-up of 3.3 years (IQR 1.2, 6.3), incident major bleeds, predominantly gastrointestinal, occurred in 254 patients (10.8 % of the cohort) and in 19.9 % of those with baseline platelets < 50,000/mu l. Incident severe thrombocytopenia occurred in 315 patients (13.4 % of cohort) and in 40.7 % of those with baseline platelet counts between 50,000 and 100,000/mu l. Baseline platelet counts between 50,000 and 100,000/mu l independently predicted bleeding [adjusted HR 2.89 (1.76, 4.73) p < 0.001] as did esophageal varices, hemoglobin a parts per thousand currency sign9.9 g %, and INR 1.4-2.0. Incident severe thrombocytopenia and minimum platelet counts < 25,000/mu l each associated with bleeding episodes, but the average of minimum platelet counts recorded for those who bled was 76,000/mu l. Among veteran patients with non-hepatitis C-related CLD, baseline platelet counts of 50,000 to 100,000/mu l increased subsequent risks for both incident severe thrombocytopenia and major bleeding events. Whereas associations between severe thrombocytopenia and bleeding most likely reflect CLD severity, liver-related coagulopathies, and co-morbid bleeding risks, interventions to enhance platelet production may be beneficial for such patients. C1 [Hermos, John A.; Altincatal, Arman; Smoot, Kyle J.; Cho, Kelly; Gagnon, David R.; Lawler, Elizabeth V.] VA Boston Healthcare Syst 151MAV, Massachusetts Vet Epidemiol Res & Informat Ctr MA, VA Cooperat Studies Program, Boston, MA 02130 USA. [Hermos, John A.; Weber, H. Christian] Boston Univ, Sch Med, Boston, MA 02118 USA. [Weber, H. Christian] VA Boston Healthcare Syst, Dept Med, Gastroenterol Sect, Boston, MA USA. [Grotzinger, Kelly] GlaxoSmithKline, Philadelphia, PA USA. [Cho, Kelly; Lawler, Elizabeth V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Hermos, JA (reprint author), VA Boston Healthcare Syst 151MAV, Massachusetts Vet Epidemiol Res & Informat Ctr MA, VA Cooperat Studies Program, 150 S Huntington Ave, Boston, MA 02130 USA. EM john.hermos@va.gov; aa2228@caa.columbia.edu; christian.weber@va.gov; kelly.m.grotzinger@gsk.com; kyle.smoot@va.gov; kelly.cho@va.gov; david.gagnon@va.gov; elizabeth.lawler@gmail.com OI Gagnon, David/0000-0002-6367-3179 FU VA Cooperative Studies Program, Massachusetts Veterans Epidemiologic Research and Information Center (MAVERIC); VA Boston Healthcare System, Boston, MA; GlaxoSmithKline, Philadelphia, PA FX The authors acknowledge the programming support of Galena Sokolovskaya. The study was supported by core funds of the VA Cooperative Studies Program, Massachusetts Veterans Epidemiologic Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, and from GlaxoSmithKline, Philadelphia, PA. NR 25 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2013 VL 58 IS 2 BP 562 EP 573 DI 10.1007/s10620-012-2404-0 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094UZ UT WOS:000315291100038 PM 23010745 ER PT J AU Wu, Y Ahmed, A Kamal, A AF Wu, Ying Ahmed, Aijaz Kamal, Ahmad TI Donor Diabetes Mellitus Is an Independent Risk Factor for Graft Loss in HCV Positive but Not HCV Negative Liver Transplant Recipients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Liver transplantation; Hepatitis C; Liver donor; Diabetes mellitus type II ID INFECTION AB Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients. We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes. Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts. Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival. C1 [Wu, Ying] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ahmed, Aijaz; Kamal, Ahmad] Stanford Univ, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Kamal, Ahmad] Santa Clara Valley Med Ctr, Div Gastroenterol, San Jose, CA 95128 USA. RP Wu, Y (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM yingny@gmail.com FU Health Resources and Services Administration [234-2005-370011C]; Stanford University Gastroenterology Division FX This work was also supported by the Health Resources and Services Administration (contract 234-2005-370011C). There was no pharmaceutical and industry support. The funding source was Stanford University Gastroenterology Division. NR 11 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2013 VL 58 IS 2 BP 574 EP 578 DI 10.1007/s10620-012-2345-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094UZ UT WOS:000315291100039 PM 22923335 ER PT J AU Pennathur, PR Thompson, D Abernathy, JH Martinez, EA Pronovost, PJ Kim, GR Bauer, LC Lubomski, LH Marsteller, JA Gurses, AP AF Pennathur, Priyadarshini R. Thompson, David Abernathy, James H., III Martinez, Elizabeth A. Pronovost, Peter J. Kim, George R. Bauer, Laura C. Lubomski, Lisa H. Marsteller, Jill A. Gurses, Ayse P. TI Technologies in the wild (TiW): human factors implications for patient safety in the cardiovascular operating room SO ERGONOMICS LA English DT Article DE patient safety; technology; hazards; cognition; cardiac operating room ID CARDIAC-SURGERY; HEALTH-CARE; EQUIPMENT; CONSEQUENCES; INFORMATION; HAZARDS; SYSTEM; ERRORS; COMMUNICATION; FAILURES AB We describe different sources of hazards from cardiovascular operating room (CVOR) technologies, how hazards propagate in the CVOR and their impact on cognitive processes. Previous studies have examined hazards from poor design of a specific CVOR technology. However, the impact of different CVOR technologies functioning in context is not clearly understood. In addition, the impact of non-design hazards in technology devices is unclear. Our study identified hazards from organisational, physical/environmental elements, in addition to design of technology in a CVOR. We used observations, follow-up interviews and photographs. With qualitative analyses, we categorised the different hazard sources and their potential impact on cognitive processes. Patient safety can be built into technologies by incorporating user needs in design, decision-making and implementation of medical technologies. Practitioner summary: Effective design and implementation of technology in a safety-critical system requires prospective understanding of technology-related hazards. Our research fills this gap by studying different technologies in context of a CVOR using observations. Qualitative analyses identified different sources for technology-related hazards besides design, and their impact on cognitive processes. C1 [Pennathur, Priyadarshini R.] Univ Iowa, Dept Mech & Ind Engn, Iowa City, IA 52242 USA. [Thompson, David; Pronovost, Peter J.; Bauer, Laura C.; Lubomski, Lisa H.; Marsteller, Jill A.; Gurses, Ayse P.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Thompson, David; Martinez, Elizabeth A.; Pronovost, Peter J.; Kim, George R.; Lubomski, Lisa H.; Marsteller, Jill A.; Gurses, Ayse P.] Johns Hopkins Univ, Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD USA. [Abernathy, James H., III] Med Univ S Carolina, Div Cardiothorac Anesthesiol, Charleston, SC 29425 USA. [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Pronovost, Peter J.; Marsteller, Jill A.; Gurses, Ayse P.] Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Pronovost, Peter J.; Kim, George R.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Kim, George R.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Kim, George R.; Gurses, Ayse P.] Johns Hopkins Univ, Sch Med, Div Hlth Sci Informat, Baltimore, MD USA. RP Pennathur, PR (reprint author), Univ Iowa, Dept Mech & Ind Engn, Iowa City, IA 52242 USA. EM prp.uiowa@gmail.com FU Society of Cardiovascular Anesthesiologists (SCA) Foundation; SCA Foundation; Agency for Healthcare Research and Quality [K01HS018762] FX This study was supported by the Society of Cardiovascular Anesthesiologists (SCA) Foundation for the LENS Project. The FOCUS Initiative is a collaborative project of the Society of Cardiovascular Anesthesiologists, the SCA Foundation and the Johns Hopkins University Quality and Safety Research Group. FOCUS is funded exclusively by the SCA Foundation. Dr. Gurses was partially supported by a grant from the Agency for Healthcare Research and Quality (K01HS018762). We thank Ms. Christine Holzmueller for her assistance in editing this manuscript. NR 46 TC 12 Z9 12 U1 3 U2 22 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0014-0139 J9 ERGONOMICS JI Ergonomics PD FEB 1 PY 2013 VL 56 IS 2 BP 205 EP 219 DI 10.1080/00140139.2012.757655 PG 15 WC Engineering, Industrial; Ergonomics; Psychology, Applied; Psychology SC Engineering; Psychology GA 092WZ UT WOS:000315155000005 PM 23384283 ER PT J AU Sommers, R Goold, SD McGlynn, EA Pearson, SD Danis, M AF Sommers, Roseanna Goold, Susan Dorr McGlynn, Elizabeth A. Pearson, Steven D. Danis, Marion TI Focus Groups Highlight That Many Patients Object To Clinicians' Focusing On Costs SO HEALTH AFFAIRS LA English DT Article ID HEALTH-CARE; PHYSICIANS; DECISIONS AB Having patients weigh costs when making medical decisions has been proposed as a way to rein in health care spending. We convened twenty-two focus groups of people with insurance to examine their willingness to discuss health care costs with clinicians and consider costs when deciding among nearly comparable clinical options. We identified the following four barriers to patients' taking cost into account: a preference for what they perceive as the best care, regardless of expense; inexperience with making trade-offs between health and money; a lack of interest in costs borne by insurers and society as a whole; and noncooperative behavior characteristic of a "commons dilemma," in which people act in their own self-interest although they recognize that by doing so, they are depleting limited resources. Surmounting these barriers will require new research in patient education, comprehensive efforts to shift public attitudes about health care costs, and training to prepare clinicians to discuss costs with their patients. C1 [Sommers, Roseanna] Yale Univ, Sch Law, New Haven, CT 06520 USA. [Goold, Susan Dorr] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Goold, Susan Dorr] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [McGlynn, Elizabeth A.] Kaiser Permanente Ctr Effectiveness & Safety Res, Oakland, CA USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. [Danis, Marion] NIH, Sect Eth & Hlth Policy, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Danis, Marion] NIH, Eth Consultat Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Sommers, R (reprint author), Yale Univ, Sch Law, New Haven, CT 06520 USA. EM mdanis@nih.gov OI Goold, Susan Dorr/0000-0002-0258-9774 FU Office of the Director; Department of Bioethics at the National Institutes of Health FX An earlier version of this article was presented at the 2012 annual meeting of the American Society for Bioethics and Humanities, Washington, D. C., October 21, 2012. This project was funded by the Office of the Director and the Department of Bioethics at the National Institutes of Health. The authors thank Beverly Weidmer, Shirley Chen, Jean Logan, and Greer Donley for assistance with the survey design, data collection, and data coding. The views expressed here are those of the authors and do not necessarily reflect the policies of the American Medical Association, the National Institutes of Health, or the Department of Health and Human Services. NR 23 TC 20 Z9 20 U1 0 U2 13 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD FEB PY 2013 VL 32 IS 2 BP 338 EP 346 DI 10.1377/hlthaff.2012.0686 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 093QQ UT WOS:000315206900019 PM 23381527 ER PT J AU Halpern, SD Loewenstein, G Volpp, KG Cooney, E Vranas, K Quill, CM McKenzie, MS Harhay, MO Gabler, NB Silva, T Arnold, R Angus, DC Bryce, C AF Halpern, Scott D. Loewenstein, George Volpp, Kevin G. Cooney, Elizabeth Vranas, Kelly Quill, Caroline M. McKenzie, Mary S. Harhay, Michael O. Gabler, Nicole B. Silva, Tatiana Arnold, Robert Angus, Derek C. Bryce, Cindy TI Default Options In Advance Directives Influence How Patients Set Goals For End-Of-Life Care SO HEALTH AFFAIRS LA English DT Article ID TREATMENT PREFERENCES; DECISION-MAKING; MEDICAL-CARE; HEALTH-CARE; CARDIOPULMONARY-RESUSCITATION; ASYMMETRIC PATERNALISM; BEHAVIORAL ECONOMICS; FAMILY; OUTCOMES; SATISFACTION AB Although decisions regarding end-of-life care are personal and important, they may be influenced by the ways in which options are presented. To test this hypothesis, we randomly assigned 132 seriously ill patients to complete one of three types of advance directives. Two types had end-of-life care options already checked-a default choice-but one of these favored comfort-oriented care, and the other, life-extending care. The third type was a standard advance directive with no options checked. We found that most patients preferred comfort-oriented care, but the defaults influenced those choices. For example, 77 percent of patients in the comfort-oriented group retained that choice, while 43 percent of those in the life-extending group rejected the default choice and selected comfort-oriented care instead. Among the standard advance directive group, 61 percent of patients selected comfort-oriented care. Our findings suggest that patients may not hold deep-seated preferences regarding end-of-life care. The findings provide motivation for future research examining whether using default options in advance directives may improve important outcomes, including patients' receipt of wanted and unwanted services, resource use, survival, and quality of life. C1 [Halpern, Scott D.] Univ Penn, Fostering Improvement End Of Life Decis Sci Progr, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Wharton Sch, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Vranas, Kelly] Philadelphia Vet Affairs Med Ctr, Med Intens Care Unit, Philadelphia, PA USA. [Quill, Caroline M.; McKenzie, Mary S.] Hosp Univ Penn, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Harhay, Michael O.] Univ Penn, Philadelphia, PA 19104 USA. [Gabler, Nicole B.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Silva, Tatiana] Univ Mannheim, Mannheim, Germany. [Arnold, Robert] Univ Pittsburgh, Inst Doctor Patient Commun, Pittsburgh, PA 15260 USA. [Angus, Derek C.] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illness, Pittsburgh, PA 15260 USA. [Bryce, Cindy] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Halpern, SD (reprint author), Univ Penn, Fostering Improvement End Of Life Decis Sci Progr, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu RI Angus, Derek/E-9671-2012; OI Bryce, Cindy/0000-0001-6356-6675 FU Greenwall Foundation; Kornfeld Foundation; Leonard Davis Institute of Health Economics at the University of Pennsylvania; Center for Excellence in Cancer Communication Research of the University of Michigan; Center for Excellence in Cancer Communication Research of the University of Pennsylvania FX This work was supported by research grants from the Greenwall Foundation, Kornfeld Foundation, Leonard Davis Institute of Health Economics at the University of Pennsylvania, and Center for Excellence in Cancer Communication Research of the Universities of Michigan and Pennsylvania. The authors thank Susan Metzger for her assistance with patient recruitment. NR 45 TC 28 Z9 28 U1 2 U2 23 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD FEB PY 2013 VL 32 IS 2 BP 408 EP 417 DI 10.1377/hlthaff.2012.0895 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 093QQ UT WOS:000315206900027 PM 23381535 ER PT J AU Prabhakar, S Taherian, M Gianni, D Conlon, TJ Fulci, G Brockmann, J Stemmer-Rachamimov, A Sena-Esteves, M Breakefield, XO Brenner, GJ AF Prabhakar, Shilpa Taherian, Mehran Gianni, Davide Conlon, Thomas J. Fulci, Giulia Brockmann, Jillian Stemmer-Rachamimov, Anat Sena-Esteves, Miguel Breakefield, Xandra O. Brenner, Gary J. TI Regression of Schwannomas Induced by Adeno-Associated Virus-Mediated Delivery of Caspase-1 SO HUMAN GENE THERAPY LA English DT Article ID SELF-COMPLEMENTARY VECTORS; NF2 TUMOR-SUPPRESSOR; CELL-DEATH; PHASE-I; MOLECULAR CHARACTERIZATION; NEUROFIBROMATOSIS TYPE-2; NERVOUS-SYSTEM; GENE-THERAPY; DISEASE; AAV AB Schwannomas are tumors formed by proliferation of dedifferentiated Schwann cells. Patients with neurofibromatosis 2 (NF2) and schwannomatosis develop multiple schwannomas in peripheral and cranial nerves. Although benign, these tumors can cause extreme pain and compromise sensory/motor functions, including hearing and vision. At present, surgical resection is the main treatment modality, but it can be problematic because of tumor inaccessibility and risk of nerve damage. We have explored gene therapy for schwannomas, using a model in which immortalized human NF2 schwannoma cells expressing a fluorescent protein and luciferase are implanted in the sciatic nerve of nude mice. Direct injection of an adeno-associated virus (AAV) serotype 1 vector encoding caspase-1 (ICE) under the Schwann-cell specific promoter, P0, leads to regression of these tumors with essentially no vector-mediated neuropathology, and no changes in sensory or motor function. In a related NF2 xenograft model designed to cause measurable pain behavior, the same gene therapy leads to tumor regression and concordant resolution of tumor-associated pain. This AAV1-P0-ICE vector holds promise for clinical treatment of schwannomas by direct intratumoral injection to achieve reduction in tumor size and normalization of neuronal function. C1 [Prabhakar, Shilpa; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Prabhakar, Shilpa; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Prabhakar, Shilpa; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Taherian, Mehran; Brenner, Gary J.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Gianni, Davide; Sena-Esteves, Miguel] Univ Massachusetts, Dept Neurol, Worcester, MA 01655 USA. [Gianni, Davide; Sena-Esteves, Miguel] Univ Massachusetts, Gene Therapy Ctr, Worcester, MA 01655 USA. [Conlon, Thomas J.] Univ Florida, Dept Pediat, Gainesville, FL 32611 USA. [Conlon, Thomas J.] Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL 32611 USA. [Fulci, Giulia] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Brockmann, Jillian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brenner, GJ (reprint author), MGH Ctr Pain Med, WAC 334,15 Parkman St, Boston, MA 02114 USA. EM gjbrenner@partners.org FU NIH/NINDS [NS24279]; DOD [NF060106] FX The authors thank Dr. Okay Saydam, Ozlem Senol, Arda Mirzak, and Mehmet Fatih Bolukbasi for help in generating the HEI-193FC line; Hae-Sook Shin for assistance with behavioral testing; and Ahmed Hassad for general technical assistance. The authors thank Kirsten E. Erger at the University of Florida Gene Therapy Center Toxicology Core for work on the DNA isolation and real-time PCR for vector biodistribution. The authors thank Leora Cramer at the Pathology Laboratory for work on the histology. The authors thank Ms. Suzanne McDavitt for skilled editorial assistance. This work was supported by NIH/NINDS grant NS24279 (X.O.B., A. S.) and DOD NF060106 (M. S. and G.J.B.). NR 47 TC 2 Z9 2 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB PY 2013 VL 24 IS 2 BP 152 EP 162 DI 10.1089/hum.2012.094 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 093MS UT WOS:000315196600005 PM 23140466 ER PT J AU Win, AK Lindor, NM Winship, I Tucker, KM Buchanan, DD Young, JP Rosty, C Leggett, B Giles, GG Goldblatt, J Macrae, FA Parry, S Kalady, MF Baron, JA Ahnen, DJ Le Marchand, L Gallinger, S Haile, RW Newcomb, PA Hopper, JL Jenkins, MA AF Win, Aung Ko Lindor, Noralane M. Winship, Ingrid Tucker, Katherine M. Buchanan, Daniel D. Young, Joanne P. Rosty, Christophe Leggett, Barbara Giles, Graham G. Goldblatt, Jack Macrae, Finlay A. Parry, Susan Kalady, Matthew F. Baron, John A. Ahnen, Dennis J. Le Marchand, Loic Gallinger, Steven Haile, Robert W. Newcomb, Polly A. Hopper, John L. Jenkins, Mark A. TI Risks of Colorectal and Other Cancers After Endometrial Cancer for Women With Lynch Syndrome SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DNA MISMATCH REPAIR; GERMLINE MUTATIONS; MOLECULAR ANALYSIS; FAMILY REGISTRY; MSH6 MUTATION; COLON-CANCER; CARRIERS; HNPCC; NONCARRIERS; GUIDELINES AB Background Lynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer. We estimated cancer risks following an endometrial cancer diagnosis for women carrying MMR gene mutations. Methods We obtained data from the Colon Cancer Family Registry for a cohort of 127 women who had a diagnosis of endometrial cancer and who carried a mutation in one of four MMR genes (30 carried a mutation in MLH1, 72 in MSH2, 22 in MSH6, and 3 in PMS2). We used the Kaplan-Meier method to estimate 10- and 20-year cumulative risks for each cancer. We estimated the age-, country-, and calendar period-specific standardized incidence ratios (SIRs) for each cancer, compared with the general population. Results Following endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers: colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%); cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%); urinary bladder cancer (9%, 95% CI = 2% to 17%); and breast cancer (11%, 95% CI = 4% to 19%). Compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (SIR = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14). Conclusions Women with Lynch syndrome who are diagnosed with endometrial cancer have increased risks of several cancers, including breast cancer. J Natl Cancer Inst;2013;105:274-279 C1 [Win, Aung Ko; Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia. [Winship, Ingrid] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA. [Winship, Ingrid; Macrae, Finlay A.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Tucker, Katherine M.] Prince Wales Hosp, Hereditary Canc Clin, Randwick, NSW 2031, Australia. [Buchanan, Daniel D.; Young, Joanne P.; Rosty, Christophe] Queensland Inst Med Res, Canc & Populat Studies Grp, Herston, Qld 4006, Australia. [Leggett, Barbara] Royal Brisbane & Womens Hosp Res Fdn, Queensland Inst Med Res, Clin Res Ctr, Conjoint Gastroenterol Lab,Pathol Queensland, Herston, Qld, Australia. [Rosty, Christophe] Univ Queensland, Dept Mol & Cellular Pathol, Herston, Qld, Australia. [Leggett, Barbara] Univ Queensland, Sch Med, Herston, Qld, Australia. [Leggett, Barbara] Royal Brisbane & Womens Hosp, Dept Gastroenterol & Hepatol, Brisbane, Qld, Australia. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Goldblatt, Jack] Univ Western Australia, Genet Serv Western Australia, Perth, WA 6009, Australia. [Goldblatt, Jack] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. [Parry, Susan] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Parry, Susan] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand. [Kalady, Matthew F.] Cleveland Clin, Dept Colorectal Surg, Inst Digest Dis, Cleveland, OH 44106 USA. [Kalady, Matthew F.] Cleveland Clin, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44106 USA. [Baron, John A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver VA Med Ctr, Denver, CO USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gallinger, Steven] Canc Care Ontario, Toronto, ON, Canada. [Haile, Robert W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Jenkins, MA (reprint author), Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Level 3,207 Bouverie St, Parkville, Vic 3010, Australia. EM m.jenkins@unimelb.edu.au RI Gallinger, Steven/E-4575-2013; Rosty, Christophe/F-1796-2010; Jenkins, Mark/P-7803-2015; Leggett, Barbara/D-3579-2011; OI Jenkins, Mark/0000-0002-8964-6160; Giles, Graham/0000-0003-4946-9099; Win, Aung Ko/0000-0002-2794-5261; Buchanan, Daniel/0000-0003-2225-6675; Winship, Ingrid/0000-0001-8535-6003 FU National Cancer Institute, National Institutes of Health under RFA [CA-95-011]; Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia FX This work was supported by the National Cancer Institute, National Institutes of Health under RFA CA-95-011, and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators. AKW is supported by the Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia. JLH is a National Health and Medical Research Council Australia Fellow. MAJ is a National Health and Medical Research Council Senior Research Fellow. JPY is a Cancer Council Queensland Senior Research Fellow. CR is a Jass Pathology Fellow. NR 34 TC 36 Z9 39 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 4 BP 274 EP 279 DI 10.1093/jnci/djs525 PG 6 WC Oncology SC Oncology GA 093PD UT WOS:000315202900008 PM 23385444 ER PT J AU Gamazon, ER Pinto, N Konkashbaev, A Im, HK Diskin, SJ London, WB Maris, JM Dolan, ME Cox, NJ Cohn, SL AF Gamazon, Eric R. Pinto, Navin Konkashbaev, Anuar Im, Hae Kyung Diskin, Sharon J. London, Wendy B. Maris, John M. Dolan, M. Eileen Cox, Nancy J. Cohn, Susan L. TI Trans-population Analysis of Genetic Mechanisms of Ethnic Disparities in Neuroblastoma Survival SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY NUMBER; CANCER; LOCUS AB Background Black patients with neuroblastoma have a higher prevalence of high-risk disease and worse outcome than white patients. We sought to investigate the relationship between genetic variation and the disparities in survival observed in neuroblastoma. Methods The analytic cohort was composed of 2709 patients. Principal components were used to assign patients to genomic ethnic clusters for survival analyses. Locus-specific ancestry was calculated for use in association analysis. The shorter spans of linkage disequilibrium in African populations may facilitate the fine mapping of causal variants in regions previously implicated by genome-wide association studies conducted primarily in patients of European descent. Thus, we evaluated 13 single nucleotide polymorphisms known to be associated with susceptibility to high-risk neuroblastoma from genome-wide association studies and all variants with highly divergent allele frequencies in reference African and European populations near the known susceptibility loci. All statistical tests were two-sided. Results African genomic ancestry was associated with high-risk neuroblastoma (P = .007) and lower event-free survival (P = .04, hazard ratio = 1.4, 95% confidence interval = 1.05 to 1.80). rs1033069 within SPAG16 (sperm associated antigen 16) was determined to have higher risk allele frequency in the African reference population and statistically significant association with high-risk disease in patients of European and African ancestry (P = 6.42 x 10(-5), false discovery rate < 0.0015) in the overall cohort. Multivariable analysis using an additive model demonstrated that the SPAG16 single nucleotide polymorphism contributes to the observed ethnic disparities in high-risk disease and survival. Conclusions Our study demonstrates that common genetic variation influences neuroblastoma phenotype and contributes to the ethnic disparities in survival observed and illustrates the value of trans-population mapping. J Natl Cancer Inst;2013;105:302-309 C1 [Gamazon, Eric R.; Konkashbaev, Anuar; Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Pinto, Navin; Cohn, Susan L.] Univ Chicago, Dept Pediat, Sect Pediat Hematol Oncol, Chicago, IL 60637 USA. [Im, Hae Kyung] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Dolan, M. Eileen] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Diskin, Sharon J.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Diskin, Sharon J.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Diskin, Sharon J.; Maris, John M.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [London, Wendy B.] Harvard Univ, Dana Farber Harvard Canc Ctr, Boston Childrens Hosp, Boston, MA 02115 USA. [London, Wendy B.] Childrens Oncol Grp Stat & Data Ctr, Arcadia, CA USA. RP Cox, NJ (reprint author), Univ Chicago, Med Genet Sect, 900 E 57th St,Rm 3220F, Chicago, IL 60637 USA. EM ncox@medicine.bsd.uchicago.edu; scohn@peds.bsd.uchicago.edu OI Cohn, Susan/0000-0001-5749-7650; Gamazon, Eric/0000-0003-4204-8734 FU National Institutes of Health [U01 GM61393, R01 MH090937, U01 HG005773, R01 CA078545]; Alex's Lemonade Stand; Children's Neuroblastoma Cancer Foundation; Elise Anderson Fund; Neuroblastoma Children's Cancer Society; Little Heroes Cancer Research Foundation; St. Baldrick's Foundation; Cancer Research Foundation FX This research was funded by the National Institutes of Health (U01 GM61393 [to MED and NJC], R01 MH090937 [to MED], U01 HG005773 [to NJC], R01 MH090937 [to NJC], and R01 CA078545 [to JMM]; Alex's Lemonade Stand (to SLC); Children's Neuroblastoma Cancer Foundation (to SLC); Elise Anderson Fund (to SLC); Neuroblastoma Children's Cancer Society (to SLC); Little Heroes Cancer Research Foundation(to SLC); St. Baldrick's Foundation (to NP); and Cancer Research Foundation (to NP). NR 34 TC 13 Z9 13 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 4 BP 302 EP 309 DI 10.1093/jnci/djs503 PG 8 WC Oncology SC Oncology GA 093PD UT WOS:000315202900011 PM 23243203 ER PT J AU Kandala, J Upadhyay, GA Altman, RK Bose, A Heist, EK Mela, T Singh, JP AF Kandala, Jagdesh Upadhyay, Gaurav A. Altman, Robert K. Bose, Abhishek Heist, E. Kevin Mela, Theofanie Singh, Jagmeet P. TI Electrical Delay in Apically Positioned Left Ventricular Leads and Clinical Outcome After Cardiac Resynchronization Therapy SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; heart failure; lead electrical delay; LV lead position; LV remodeling ID CHRONIC HEART-FAILURE; BUNDLE-BRANCH BLOCK; ACTIVATION AB Electrical Delay in Apically Positioned LV Leads.Introduction: In recent studies, an anatomical apical left ventricular (LV) lead pacing location has been associated with deleterious outcome after cardiac resynchronization therapy (CRT). The differential impact of the LV lead electrical location in these patients remains unknown. Methods and Results: Thirty-one consecutive CRT patients (mean age 71.7 +/- 12.7 years, 55% left bundle-branch block [LBBB] morphology) with an apical LV lead and LV lead electrical delay (LVLED) were studied. Anatomical LV lead location was determined via review of coronary venography and chest radiographs. Electrical location was assessed through intraprocedural LVLED measurement. Patients were dichotomized into either long LVLED (LVLED 50% of QRS) or short LVLED groups (LVLED < 50%). Patients in the long LVLED group demonstrated significantly greater freedom from a primary composite endpoint of all-cause death, heart failure hospitalization, and cardiac transplantation at 2 years (81% vs 30%, P = 0.007 vs short LVLED patients). Longer LVLED was also associated with more favorable LV remodeling (LV end-systolic volume 41.9 +/- 10.3 mL vs 4.3 +/- 17.2 mL; P = 0.05), and greater improvement in LV ejection fraction (+9.4 +/- 2.9% vs +2.3 +/- 7.5%; P = 0.04). Even after multivariate adjustment, LVLED remained an independent predictor of the primary composite endpoint (HR 0.47, P = 0.031). Conclusions: Electrical lead localization, as estimated by LVLED 50%, is associated with improved long-term clinical outcome and measures of LV remodeling in patients with apical LV leads. Intraprocedural LVLED assessment may provide incremental utility in targeting lead placement even in conventionally unfavorable anatomical segments.(J Cardiovasc Electrophysiol, Vol. 24, pp. 182-187, February 2013) C1 [Kandala, Jagdesh; Upadhyay, Gaurav A.; Altman, Robert K.; Bose, Abhishek; Heist, E. Kevin; Mela, Theofanie; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561 FU Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology of the Heart Rhythm Society; Biotronik; Boston Scientific Corp.; Sorin; St. Jude Medical; Medtronic Inc. FX J. Kandala, R. K. Altman, and A. Bose report no significant financial disclosures. G. A. Upadhyay received salary support from the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology of the Heart Rhythm Society. E. K. Heist reports Biotronik (honoraria/research grants), Boston Scientific Corp. (consultant/honoraria/research grants), Sorin (consultant/honoraria/research grants), and St. Jude Medical (consultant/honoraria/research grants). T. Mela reports Boston Scientific Corp. (honoraria), Medtronic Inc. (honoraria), and St Jude Medical (honoraria). J. P. Singh reports St. Jude Medical (consultant/honoraria/research grants), Medtronic Inc. (consultant/honoraria/research grants), Boston Scientific Corp. (consultant/honoraria/research grants), Biotronik (consultant/honoraria/research grants), Sorin Group (consultant/honoraria), CardioInsight Inc. (consultant), and Respicardia Inc. (consultant). NR 25 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2013 VL 24 IS 2 BP 182 EP 187 DI 10.1111/j.1540-8167.2012.02428.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 083NF UT WOS:000314470500014 PM 22966852 ER PT J AU Dhanani, NM Jiang, YD AF Dhanani, Nadya M. Jiang, Yandong TI Olfactory disorders after general anesthesia Reply SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter C1 [Dhanani, Nadya M.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Dhanani, NM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM yjiang@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2013 VL 25 IS 1 BP 73 EP 74 DI 10.1016/j.jclinane.2012.10.002 PG 2 WC Anesthesiology SC Anesthesiology GA 091RM UT WOS:000315067500017 PM 23246498 ER PT J AU Cather, C Dyer, MA Burrell, HA Hoeppner, B Goff, DC Evins, AE AF Cather, Corinne Dyer, Michael A. Burrell, Heather A. Hoeppner, Bettina Goff, Donald C. Evins, A. Eden TI An Open Trial of Relapse Prevention Therapy for Smokers With Schizophrenia SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE schizophrenia; severe mental illness; smoking cessation; nicotine replacement therapy; bupropion; cognitive behavioral therapy; relapse prevention ID PLACEBO-CONTROLLED TRIAL; BUPROPION SUSTAINED-RELEASE; SMOKING-CESSATION; CIGARETTE-SMOKING; DOUBLE-BLIND; NICOTINE; MORTALITY; NORMALIZATION; NONSMOKERS; DISORDERS AB Objective: Following successful smoking cessation, smokers with schizophrenia are vulnerable to relapse shortly after treatment discontinuation. Our objective was to assess the feasibility and effectiveness of a 12-month relapse prevention intervention in recently abstinent smokers with schizophrenia. Method: Adult outpatient smokers with schizophrenia received weekly cognitive-behavioral therapy groups, bupropion slow-release, transdermal nicotine patch, and nicotine gum or lozenge for 3 months. Subjects with 7-day point prevalence abstinence at month 3 received an additional 12 months (months 4 through 15) of therapy with bupropion, transdermal nicotine patch, and nicotine gum/lozenge in conjunction with relapse preventionbased cognitive-behavioral therapy groups that were held weekly in month 4, biweekly in months 5 and 6, and monthly in months 7 through 15. Results: Seventeen of 41 participants (41.5%) attained biochemically verified self-report of 7-day point prevalence abstinence at the end of 3 months of treatment and entered relapse prevention treatment. There was an 81% attendance rate at relapse prevention groups. At the end of the 12-month relapse prevention phase (month 15 overall), 11 of 17 (64.7%) demonstrated biochemically verified 7-day point prevalence abstinence, and 10 of 17 (58.8%) reported 4-week continuous abstinence. Almost one-quarter of the sample (23.5%) demonstrated long-term prolonged abstinence through the end of the trial. There were no clinically detected cases of psychiatric symptom exacerbation. One participant, who was managed as an outpatient, self-reported psychiatric symptom exacerbation in the interim period between study visits. Conclusions: Extended-duration smoking cessation treatment is well tolerated and may improve smoking outcomes for recently abstinent smokers with schizophrenia. Controlled trials are warranted. C1 [Cather, Corinne; Dyer, Michael A.; Burrell, Heather A.; Goff, Donald C.; Evins, A. Eden] Massachusetts Gen Hosp, Schizophrenia Program, Dept Psychiat, Boston, MA 02114 USA. [Cather, Corinne; Hoeppner, Bettina; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Cather, Corinne; Dyer, Michael A.; Burrell, Heather A.; Goff, Donald C.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ccather@partners.org FU NIDA NIH HHS [K01 DA027097, K23 DA000510, K24 DA030443, L30 DA025511]; NIMH NIH HHS [K24 MH002025] NR 38 TC 10 Z9 11 U1 2 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PD FEB 1 PY 2013 VL 9 IS 1 BP 87 EP 93 DI 10.1080/15504263.2012.749559 PG 7 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 092XP UT WOS:000315156600011 PM 23750123 ER PT J AU Shin, SS Bales, JW Yan, HQ Kline, AE Wagner, AK Lyons-Weiler, J Dixon, CE AF Shin, Samuel S. Bales, James W. Yan, Hong Q. Kline, Anthony E. Wagner, Amy K. Lyons-Weiler, James Dixon, C. Edward TI The Effect of Environmental Enrichment on Substantia Nigra Gene Expression after Traumatic Brain Injury in Rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE dopamine; EE; microarray; TBI ID CLOSED HEAD-INJURY; MEDIATED FUNCTIONAL IMPROVEMENT; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CORTICAL IMPACT; WATER MAZE PERFORMANCE; LONG-TERM POTENTIATION; PARKINSONS-DISEASE; MESSENGER-RNA; AXONAL INJURY; NEUROBEHAVIORAL RECOVERY AB Experimental investigations into the effects of traumatic brain injury (TBI) have demonstrated significant alterations in dopaminergic systems. Dopaminergic fibers originating within the substantia nigra and ventral tegmental area (VTA) are important for reward learning, addiction, movement, and behavior. However, little is known about the effect of TBI on substantia nigra and VTA function. Environmental enrichment (EE) has been shown to improve functional outcome after TBI, and a number of studies suggest that it may exert some benefits via dopaminergic signaling. To better understand the role of dopamine in chronic TBI pathophysiology and the effect of EE, we examined the mRNA expression profile within the substantia nigra and VTA at 4 weeks post-injury. Specifically, three comparisons were made: 1) TBI versus sham, 2) sham + EE versus sham + standard (STD) housing, and 3) TBI + EE versus TBI + STD. There were differential expressions of 25, 4, and 40 genes in these comparisons, respectively. Chronic alterations in genes post-injury within the substantia nigra and VTA included genes important for cellular membrane homeostasis and transcription. EE-induced gene alterations after TBI included genes important for signal transduction, in particular calcium signaling pathways, membrane homeostasis, and metabolism. Elucidation of these alterations in gene expression within the substantia nigra and VTA provides new insights into chronic changes in dopamine signaling post-TBI, and the potential role of EE in TBI rehabilitation. C1 [Shin, Samuel S.; Bales, James W.; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Bales, James W.; Yan, Hong Q.; Kline, Anthony E.; Wagner, Amy K.; Dixon, C. Edward] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Bales, James W.; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Bales, James W.; Yan, Hong Q.; Kline, Anthony E.; Wagner, Amy K.; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. [Kline, Anthony E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Kline, Anthony E.; Wagner, Amy K.; Dixon, C. Edward] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Lyons-Weiler, James] Univ Pittsburgh, Genom & Prote Core Labs Bioinformat Anal Core, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Dixon, CE (reprint author), Univ Pittsburgh, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM dixonec@upmc.edu OI Lyons-Weiler, James/0000-0001-9343-7508 FU National Institutes of Health (NIH) [R21NS047919, P01NS030318, R01NS060672, 5F30NS067731-03]; Pittsburgh Copeland Foundation; [R01NS060005] FX This research was supported by National Institutes of Health (NIH) grants R21NS047919, P01NS030318, R01NS060672, NIH F30 grant 5F30NS067731-03, and the Pittsburgh Copeland Foundation (CED), and R01NS060005 (AEK). NR 92 TC 9 Z9 10 U1 1 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD FEB PY 2013 VL 30 IS 4 BP 259 EP 270 DI 10.1089/neu.2012.2462 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 093CM UT WOS:000315169300003 PM 23094804 ER PT J AU Plank, RM Kubiak, DW Abdullahi, RB Ndubuka, N Nkgau, MM Dapaah-Siakwan, F Powis, KM Lockman, S AF Plank, Rebeca M. Kubiak, David W. Abdullahi, Rasak Bamidele Ndubuka, Nnamdi Nkgau, Maggie M. Dapaah-Siakwan, Fredrick Powis, Kathleen M. Lockman, Shahin TI Loss of anatomical landmarks with eutectic mixture of local anesthetic cream for neonatal male circumcision SO JOURNAL OF PEDIATRIC UROLOGY LA English DT Article DE Male circumcision; Neonatal; EMLA; Eutectic mixture of local anesthetic; Adverse events; Edema ID RANDOMIZED CONTROLLED-TRIAL; PENILE NERVE BLOCK; LIDOCAINE-PRILOCAINE CREAM; TOPICAL ANESTHESIA; HIV PREVENTION; EMLA CREAM; METHEMOGLOBINEMIA; PAIN; INFECTION; ANALGESIA AB We report two cases of newborns who developed marked local edema after application of a eutectic mixture of local anesthetic (EMLA) topical anesthetic cream for neonatal male circumcision (NMC). Although local edema and erythema are known potential side effects of EMLA cream, a common anesthetic used for NMC, the loss of landmarks precluding safe NMC has not previously been reported, and is described here. Although we cannot recommend an alternate local anesthetic for neonates with this reaction to EMLA, based on a review of the published data we think that serious systemic adverse events related to EMLA are extremely rare. (C) 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. C1 [Plank, Rebeca M.; Kubiak, David W.; Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Plank, Rebeca M.; Powis, Kathleen M.; Lockman, Shahin] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Plank, Rebeca M.; Abdullahi, Rasak Bamidele; Ndubuka, Nnamdi; Nkgau, Maggie M.; Powis, Kathleen M.; Lockman, Shahin] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Kubiak, David W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dapaah-Siakwan, Fredrick] Scottish Livingstone Hosp, Molepolole, Botswana. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Dapaah-Siakwan, Fredrick] Albert Einstein Med Ctr, Dept Pediat, Philadelphia, PA 19141 USA. RP Plank, RM (reprint author), 15 Francis St PBB A-4, Boston, MA 02115 USA. EM rplank@partners.org FU NIH from the National Institutes of Allergy and Infectious Diseases [5K23AI084579]; President's Emergency Plan for AIDS Relief (PEPFAR) [U2GPS000941-01, 08-P0157] FX Supported by NIH 5K23AI084579 from the National Institutes of Allergy and Infectious Diseases (Dr. Plank). The larger study was supported through the President's Emergency Plan for AIDS Relief (PEPFAR) grant U2GPS000941-01, Program No. 08-P0157. The content is solely the responsibility of the authors and does not necessarily represent the official views of PEPFAR or the National Institutes of Health. The study sponsors had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 29 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1477-5131 J9 J PEDIATR UROL JI J. Pediatr. Urol PD FEB PY 2013 VL 9 IS 1 BP E86 EP E90 DI 10.1016/j.jpurol.2012.09.013 PG 5 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 094SU UT WOS:000315284900026 PM 23102766 ER PT J AU Villamar, MF Fregni, F AF Villamar, Mauricio F. Fregni, Felipe TI ON THE INSUFFICIENCY OF REPORTING MASKING RESPONSE SO JOURNAL OF REHABILITATION MEDICINE LA English DT Letter ID TRIALS C1 [Villamar, Mauricio F.; Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Villamar, Mauricio F.; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Villamar, Mauricio F.] Pontifical Catholic Univ Ecuador, Sch Med, Quito, Ecuador. [Villamar, Mauricio F.] Spaulding Rehabil Hosp, Boston, MA 02114 USA. RP Villamar, MF (reprint author), Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02114 USA. EM Fregni.Felipe@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU FOUNDATION REHABILITATION INFORMATION PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 1650-1977 J9 J REHABIL MED JI J. Rehabil. Med. PD FEB PY 2013 VL 45 IS 2 BP 221 EP 222 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 093GM UT WOS:000315179700020 PM 23495381 ER PT J AU Schoenborn, NL Arbaje, AI Eubank, KJ Maynor, K Carrese, JA AF Schoenborn, Nancy L. Arbaje, Alicia I. Eubank, Kathryn J. Maynor, Kenric Carrese, Joseph A. TI Clinician Roles and Responsibilities During Care Transitions of Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE care transitions; older adults; qualitative study; clinician roles; healthcare professionals ID HOSPITAL DISCHARGE; FOLLOW-UP; COMMUNICATION; PHYSICIANS; CONTINUITY; TRIAL; OPPORTUNITIES; INTERVENTION; READMISSION; INFECTIONS AB OBJECTIVES: To identify the perceived roles and responsibilities of clinicians during care transitions of older adults. DESIGN: Qualitative study involving 1-hour in-depth semistructured interviews. Audiotapes of interviews were transcribed, coded, and analyzed, and themes and sub-themes were generated. SETTING: An acute care hospital, a skilled nursing facility, two community-based outpatient practices, and one home healthcare agency. PARTICIPANTS: Forty healthcare professionals directly involved in care transitions of older adults (18 physicians, 11 home healthcare administrative and field staff, four social workers, three nurse practitioners, three physician assistants, and one hospital case manager). MEASUREMENTS: Perspectives of healthcare professionals regarding clinicians' roles and responsibilities during care transitions were examined and described. RESULTS: Content analysis revealed several themes: components of clinicians' roles during care transitions; congruence between self- and others' perceived ideal roles but incongruence between ideal and routine roles; ambiguity in accountability in the postdischarge period; factors prompting clinicians to act closer to ideal roles; and barriers to performing ideal roles. A conceptual framework was created to summarize clinicians' roles during care transitions. CONCLUSION: This study reports differences between what healthcare professionals perceive as ideal roles of clinicians during care transitions and what clinicians actually do routinely. Certain patient and clinician factors prompt clinicians to act closer to the ideal roles. Multiple barriers interfere with consistent practice of ideal roles. Future investigations could evaluate interventions targeting various components of the conceptual framework and relevant outcomes. J Am Geriatr Soc 61:231-236, 2013. C1 [Schoenborn, Nancy L.; Arbaje, Alicia I.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. [Eubank, Kathryn J.] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA USA. [Maynor, Kenric] Geisinger Hlth Syst, Wyoming Valley Med Ctr, Dept Hospitalist Med, Wilkes Barre, PA USA. [Carrese, Joseph A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. RP Schoenborn, NL (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Geriatr Med & Gerontol, 5200 Eastern Ave,Mason F Lord Bldg,Ctr Tower,Suit, Baltimore, MD 21224 USA. EM nancyli@jhmi.edu FU Robert Wood Johnson Foundation Clinical Scholars Program; Harold Amos Medical Faculty Development Program FX This project was supported by the Robert Wood Johnson Foundation Clinical Scholars Program and Harold Amos Medical Faculty Development Program. NR 30 TC 9 Z9 9 U1 2 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2013 VL 61 IS 2 BP 231 EP 236 DI 10.1111/jgs.12084 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 094HY UT WOS:000315254800008 PM 23320747 ER PT J AU Brown, AF Vassar, SD Connor, KI Vickrey, BG AF Brown, Arleen F. Vassar, Stefanie D. Connor, Karen I. Vickrey, Barbara G. TI Collaborative Care Management Reduces Disparities in Dementia Care Quality for Caregivers with Less Education SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; caregivers; care management ID NURSING-HOME PLACEMENT; ALZHEIMERS-DISEASE; OF-CARE; INTERVENTION; OUTCOMES; HEALTH; PATIENT; BURDEN; INSTITUTIONALIZATION; PREDICTORS AB OBJECTIVES: To examine educational gradients in dementia care and whether the effect of a dementia collaborative care management intervention varied according to the educational attainment of the informal caregiver, DESIGN: Analysis of data from a cluster-randomized controlled trial. SETTING: Eighteen clinics in three healthcare organizations in southern California. PARTICIPANTS: Dyads of Medicare recipients aged 65 and older with a diagnosis of dementia and an eligible caregiver. INTERVENTION: Collaborative care management for dementia. MEASUREMENTS: Caregiver educational attainment, adherence to four dimensions of guideline-recommended processes of dementia care (assessment, treatment, education and support, and safety) before and after the intervention, and the adjusted intervention effect (IE) for each dimension stratified according to caregiver education. Each IE, was estimated by subtracting the difference between pre- and postintervention scores for the usual care participants from the difference between pre- and postintervention scores in the intervention participants. RESULTS: At baseline, caregivers with lower educational attainment provided poorer quality of dementia care for the Treatment and Education dimensions than those with more education, but less-educated caregivers had significantly more improvement after the intervention on the assessment, treatment, and safety dimensions. The IEs for those who had not graduated from high school were 44.4 for the assessment dimension, 36.9 for the treatment dimension, and 52.7 for the safety dimension, versus 29.5, 15.7, and 40.9 respectively, for college graduates (P < .001 for all three). CONCLUSIONS: Collaborative care management was associated with smaller disparities in dementia care quality between caregivers with lower educational attainment and those with more education. J Am Geriatr Soc 61:243-251, 2013. C1 [Brown, Arleen F.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. [Vassar, Stefanie D.; Connor, Karen I.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Vassar, Stefanie D.; Connor, Karen I.; Vickrey, Barbara G.] Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA. RP Brown, AF (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza,Room 205, Los Angeles, CA 90024 USA. EM abrown@mednet.ucla.edu FU California Healthcare Foundation [99-3020]; State of California Department of Aging [IG-0001-22]; State of California Department of Health Services; Alzheimer's Disease Education Initiative [00-91, 316]; Archstone Foundation [00-04-37]; University of California at Los Angeles (UCLA) Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under National Institutes of Health, National Institute on Aging [P30-AG021684]; UCLA/Drew Project EXPORT; National Center on Minority Health and Health Disparities [2P20MD000182]; National Center for Advancing Clinical Sciences; UCLA Clinical and Translational Research Institute [UL1TR000124] FX Funding for the original study was provided by the California Healthcare Foundation (99-3020), the State of California Department of Aging (IG-0001-22), the State of California Department of Health Services, the Alzheimer's Disease Education Initiative (00-91,316), and the Archstone Foundation (00-04-37). Dr. Brown received support from the University of California at Los Angeles (UCLA) Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under National Institutes of Health, National Institute on Aging Grant P30-AG021684, from UCLA/Drew Project EXPORT, National Center on Minority Health and Health Disparities, 2P20MD000182, and from the National Center for Advancing Clinical Sciences, UCLA Clinical and Translational Research Institute, UL1TR000124. The content does not necessarily represent the official views of the sponsoring organizations. NR 28 TC 4 Z9 4 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2013 VL 61 IS 2 BP 243 EP 251 DI 10.1111/jgs.12079 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 094HY UT WOS:000315254800010 PM 23320655 ER PT J AU Koyama, A Steinman, M Ensrud, K Hillier, TA Yaffe, K AF Koyama, Alain Steinman, Michael Ensrud, Kristine Hillier, Teresa A. Yaffe, Kristine TI Ten-Year Trajectory of Potentially Inappropriate Medications in Very Old Women: Importance of Cognitive Status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive function; dementia; potentially inappropriate medication; anticholinergic ID CHOLINESTERASE-INHIBITORS; BENZODIAZEPINE USE; ELDERLY-PATIENTS; CONTROLLED-TRIAL; BEERS CRITERIA; RISK-FACTORS; DRUG-USE; ANTICHOLINERGICS; IMPAIRMENT; DEMENTIA AB OBJECTIVES: To determine which older adults tend to receive potentially inappropriate medications (PIMs), how this may differ according to cognitive status, and how the trajectories of PIM use change over time. DESIGN: Ten-year longitudinal cohort study. SETTING: Three clinical sites in the United States. PARTICIPANTS: One thousand four hundred eighty-four community-dwelling women aged 75 and older. MEASUREMENTS: At follow-up, cognitive status was ascertained and classified as normal, mild cognitive impairment (MCI), or dementia. Beers 2003 criteria and other literature were used to identify PIMs from,detailed medication inventory performed at three time points. Anticholinergic load was measured using the Anticholinergic Cognitive Burden Scale (ACB), which assigns medications a value from 0 to 3 depending on anticholinergic properties. RESULTS: At baseline, 23.9% of women were taking at least one PIM and the mean +/- SD ACB score was 1.41 +/- 1.69. The most frequently reported PIMs were anticholinergics (15.2%), benzodiazepines (8.6%), and antispasmodics (8.0%). Over 10 years, PIM use increased for women with dementia (24.9-33.1%; P = .02) but remained fairly constant for women with MCI (23.9-23.0%; P = .84) and normal cognitive status (22.2-19.8%; P = .17). Mean ACB score increased significantly (P < .001) over time for all groups (dementia: 1.28-2.05; MCI: 0.98-1.66; normal: 0.99-1.48). CONCLUSION: PIM use and anticholinergic load in a community-dwelling population of older women was high, especially in women who later developed dementia. Future guidelines should limit PIM use and seek safer alternatives. J Am Geriatr Soc 61:258-263, 2013. C1 [Koyama, Alain] No Calif Inst Res & Educ, San Francisco, CA USA. [Koyama, Alain; Steinman, Michael; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Steinman, Michael] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ensrud, Kristine] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine] Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Hillier, Teresa A.] Kaiser Permanente Northwest Hawaii, Ctr Hlth Res, Honolulu, HI USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Koyama, A (reprint author), 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA. EM alain.koyama@va.gov FU National Institute of Aging (NIA) [K24 AG 031155, R01 AG 026720]; Alzheimer's Association [IIRG-08-88872]; National Institutes of Health (NIH); NIA [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576] FX Funded in part by Grants K24 AG 031155 and R01 AG 026720 from the National Institute of Aging (NIA) and Grant IIRG-08-88872 from the Alzheimer's Association. The Study of Osteoporotic Fractures is supported by the National Institutes of Health (NIH). NIA provides support under Grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. NR 30 TC 16 Z9 16 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2013 VL 61 IS 2 BP 258 EP 263 DI 10.1111/jgs.12093 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 094HY UT WOS:000315254800012 PM 23320787 ER PT J AU Thai, JN Walter, LC Eng, C Smith, AK AF Thai, Julie N. Walter, Louise C. Eng, Catherine Smith, Alexander K. TI Every Patient Is an Individual: Clinicians Balance Individual Factors When Discussing Prognosis with Diverse Frail Elderly Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE prognosis; geriatrics; end of life ID DECISION-MAKING; OLDER; LIFE; END; COMMUNICATION; MAMMOGRAPHY; BURDENS; WOMEN; CARE; AGE AB BACKGROUND: To explore clinician choice of whether to discuss prognosis with their frail older patients. DESIGN: Qualitative interview study. SETTING: Primary care clinicians were recruited from nursing homes, community-based clinics, and academic medical centers. PARTICIPANTS: Three geriatric nurse practitioners, nine geriatricians, five general internists, and three family medicine physicians with a mean age of 44 and a mean 12 years in practice. Seventeen clinicians had patient panels with 80% or more community-dwelling outpatients, 13 had patient panels with 50% or more patients aged 85 and older, and 16 had patient panels with 25% or more of patients in a minority group (Asian, African American, Hispanic). MEASUREMENTS: Clinicians were asked to describe their practice of discussing long-term (<5-year) and short-term (<1-year and 3-month) prognosis. Responses were analyzed qualitatively using constant comparison until thematic saturation was reached. RESULTS: Clinicians reported individualizing the decision to discuss prognosis with their frail older patients based on clinical circumstances. Common reasons for discussing prognosis included patient had a specific condition with a limited prognosis, to give patients time to prepare, to promote informed medical decision-making, and when patients or families prompted the conversation. Common reasons not to discuss included maintaining hope and avoiding anxiety, cognitive impairment or patient unable to understand prognosis, respect for patients' cultural values, and long-term prognosis too uncertain to be useful. CONCLUSION: Clinicians caring for frail older adults are generally willing to discuss short- but not long-term prognosis. Clinicians balance individual factors when deciding whether to discuss prognosis. J Am Geriatr Soc 61:264-269, 2013. C1 [Thai, Julie N.; Walter, Louise C.; Eng, Catherine; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. [Thai, Julie N.; Walter, Louise C.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Eng, Catherine] On Lok Lifeways, San Francisco, CA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu FU Center for Aging in Diverse Communities of the Resource Centers for Minority Aging Research program [P30-AG15272]; National Institute on Aging, National Institutes of Health; National Center for Research Resources UCSF-CTSI [UL1 RR024131]; Atlantic Philanthropies; Society of General Internal Medicine; John A. Hartford Foundation; Association of Specialty Professors FX Dr. Smith was supported by pilot Grant P30-AG15272 from the Center for Aging in Diverse Communities of the Resource Centers for Minority Aging Research program funded by the National Institute on Aging, National Institutes of Health. The National Center for Research Resources UCSF-CTSI (UL1 RR024131), Atlantic Philanthropies, the Society of General Internal Medicine, the John A. Hartford Foundation, and the Association of Specialty Professors provided additional support. NR 17 TC 8 Z9 8 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2013 VL 61 IS 2 BP 264 EP 269 DI 10.1111/jgs.12098 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 094HY UT WOS:000315254800013 PM 23320808 ER PT J AU Vorasubin, N Wu, AW Day, C Suh, JD AF Vorasubin, Nopawan Wu, Arthur W. Day, Christina Suh, Jeffrey D. TI Invasive sinonasal actinomycosis: Case Report and Literature Review SO LARYNGOSCOPE LA English DT Article DE sinonasal actinomycosis; cervicofacial actinomycosis ID SINUS ACTINOMYCOSIS; MAXILLARY SINUS; MANAGEMENT; INFECTION AB Actinomycosis is a rare anaerobic bacterial infection typically caused by Actinomyces israelii. Although part of normal flora in the oral cavity, and respiratory and digestive tracts, A israelii can give rise to pathologic infections most commonly reported in the oral cavity from odontogenic causes. We present a rare case of invasive actinomycosis presenting with extensive midface destruction involving the maxilla and paranasal sinuses, with mucosal necrosis mimicking an aggressive neoplasm. The diagnosis is usually reached only after histopathologic analysis showing characteristic sulfur granules with filamentous gram-positive, nonacid-fast bacteria. We review the literature on its epidemiology, clinical presentation, diagnosis, treatment, and prognosis. C1 [Vorasubin, Nopawan; Wu, Arthur W.; Suh, Jeffrey D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Day, Christina] W Los Angeles Vet Affairs Hosp, Dept Pathol, Los Angeles, CA USA. RP Vorasubin, N (reprint author), 10833 Le Conte Ave,62-132 CHS, Los Angeles, CA 90095 USA. EM nvorasubin@mednet.ucla.edu NR 24 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2013 VL 123 IS 2 BP 334 EP 338 DI 10.1002/lary.23477 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 090NH UT WOS:000314985400009 PM 23008010 ER PT J AU Lakhani, KR Boudreau, KJ Loh, PR Backstrom, L Baldwin, C Lonstein, E Lydon, M MacCormack, A Arnaout, RA Guinan, EC AF Lakhani, Karim R. Boudreau, Kevin J. Loh, Po-Ru Backstrom, Lars Baldwin, Carliss Lonstein, Eric Lydon, Mike MacCormack, Alan Arnaout, Ramy A. Guinan, Eva C. TI Prize-based contests can provide solutions to computational biology problems SO NATURE BIOTECHNOLOGY LA English DT Letter ID FOLDING GAME PLAYERS; INNOVATION CONTESTS; SEARCH; SYSTEM C1 [Lakhani, Karim R.; Baldwin, Carliss; Lonstein, Eric; MacCormack, Alan] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Lakhani, Karim R.; Boudreau, Kevin J.] Harvard NASA Tournament Lab, Inst Quantitat Social Sci, Boston, MA USA. [Boudreau, Kevin J.] London Business Sch, London NW1 4SA, England. [Loh, Po-Ru] MIT, Dept Math & Comp Sci, Cambridge, MA 02139 USA. [Loh, Po-Ru] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Backstrom, Lars; Lydon, Mike] TopCoder Com, Glastonbury, CT USA. [Arnaout, Ramy A.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Arnaout, Ramy A.] Beth Israel Deaconess Med Ctr, Div Clin Informat, Dept Med, Boston, MA 02215 USA. [Arnaout, Ramy A.; Guinan, Eva C.] Harvard Univ, Sch Med, Boston, MA USA. [Guinan, Eva C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lakhani, KR (reprint author), Harvard Univ, Sch Business, Boston, MA 02163 USA. EM eva_guinan@dfci.harvard.edu RI Boudreau, Kevin/A-1036-2015 OI Boudreau, Kevin/0000-0002-9029-8247 FU NCRR NIH HHS [5UL1RR025758, 5UL1RR025758-S, UL1 RR025758] NR 27 TC 41 Z9 41 U1 1 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2013 VL 31 IS 2 BP 108 EP 111 DI 10.1038/nbt.2495 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 095GG UT WOS:000315322100014 PM 23392504 ER PT J AU Weiner, MW AF Weiner, Michael W. TI Further insights into Alzheimer disease pathogenesis SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID PRIONS; TAU AB In 2012, studies of autosomal dominant Alzheimer disease (AD), late-onset AD, and a rare genetic mutation of amyloid precursor protein provided support for the critical role of amyloid in AD pathogenesis. Increasing evidence implicated cell-to-cell transmission in the spread of tau and amyloid, highlighting novel targets for therapeutic intervention. Weiner, M. W. Nat. Rev. Neurol. 9, 65-66 (2013); published online 22 January 2013; doi:10.1038/nrneurol.2012.275 C1 Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, Dept Radiol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Weiner, MW (reprint author), Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, Dept Radiol, San Francisco VA Med Ctr, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM michael.weiner@ucsf.edu NR 8 TC 17 Z9 19 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD FEB PY 2013 VL 9 IS 2 BP 65 EP 66 DI 10.1038/nrneurol.2012.275 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 094GG UT WOS:000315250400002 PM 23338285 ER PT J AU Kenton, K Mueller, ER Tarnay, C Brubaker, L Rosenman, A Smith, B Stroupe, K Bresee, C Anger, JT AF Kenton, Kimberly Mueller, Elizabeth R. Tarnay, Christopher Brubaker, Linda Rosenman, Amy Smith, Bridget Stroupe, Kevin Bresee, Catherine Anger, Jennifer T. TI COMPARATIVE EFFECTIVENESS OF ROBOTIC AND LAPAROSCOPIC SACROCOLPOPEXY FOR APICAL VAGINAL PROLAPSE: ONE YEAR OUTCOMES SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Kenton, Kimberly; Mueller, Elizabeth R.; Brubaker, Linda] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Tarnay, Christopher; Rosenman, Amy] UCLA Med Ctr, Los Angeles, CA USA. [Smith, Bridget; Stroupe, Kevin] US Dept Vet Affairs, Hines, IL USA. [Bresee, Catherine; Anger, Jennifer T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Bresee, Catherine/A-9148-2015 OI Bresee, Catherine/0000-0002-5710-4906 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 112 EP 113 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200016 ER PT J AU Cristofaro, V Yalla, SV Sullivan, MP AF Cristofaro, Vivian Yalla, Subbarao V. Sullivan, Maryrose P. TI REGULATION OF BLADDER SPONTANEOUS ACTIVITY BY INTERACTION OF CAVEOLAE AND PURINERGIC (P2X) RECEPTORS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Cristofaro, Vivian; Yalla, Subbarao V.; Sullivan, Maryrose P.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 124 EP 125 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200044 ER PT J AU Wang, ZW Cheng, ZY Cristofaro, V Sullivan, M White, M Olumi, A AF Wang, Zongwei Cheng, Zhiyong Cristofaro, Vivian Sullivan, Maryrose White, Morris Olumi, Aria TI UROTHELIUM RELEASED ATP CONTRIBUTES TO BLADDER DYSFUNCTION IN TYPE 2 DIABETES SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Wang, Zongwei; Olumi, Aria] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheng, Zhiyong; White, Morris] Childrens Hosp Boston, Div Endocrinol, Howard Hughes Med Inst, Boston, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 127 EP 127 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200049 ER PT J AU Munoz, A Boone, TB Smith, CP Salas, NA Somogyi, GT AF Munoz, Alvaro Boone, Timothy B. Smith, Christopher P. Salas, Nilson A. Somogyi, George T. TI BLADDER OVERACTIVITY FOLLOWING SPINAL CORD INJURY IS IMPROVED BY INCREASING NITRIC OXIDE LEVELS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Munoz, Alvaro; Boone, Timothy B.; Salas, Nilson A.] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Munoz, Alvaro; Smith, Christopher P.; Salas, Nilson A.; Somogyi, George T.] Baylor Coll Med, Houston, TX 77030 USA. [Boone, Timothy B.; Smith, Christopher P.] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 128 EP 129 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200053 ER PT J AU Munoz, A Boone, TB Sun, YX AF Munoz, Alvaro Boone, Timothy B. Sun, Yuxiang TI GHRELIN-SIGNALING AFFECTS NEURALLY EVOKED BLADDER CONTRACTIONS BUT NOT DETRUSOR PERFORMANCE SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Munoz, Alvaro; Boone, Timothy B.] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Munoz, Alvaro; Sun, Yuxiang] Baylor Coll Med, Houston, TX 77030 USA. [Boone, Timothy B.] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 134 EP 134 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200064 ER PT J AU Cristofaro, V Chaudhury, A Goyal, RK Sullivan, MP AF Cristofaro, Vivian Chaudhury, Arun Goyal, Raj K. Sullivan, Maryrose P. TI IMPAIRED PURINERGIC NEUROTRANSMISSION IN MYOSINVA DEFICIENT MOUSE BLADDERS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Cristofaro, Vivian; Chaudhury, Arun; Goyal, Raj K.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Sullivan, Maryrose P.] VA Boston Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 136 EP 137 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200069 ER PT J AU Polland, A Meckel, K Trop, C AF Polland, Allison Meckel, Katherine Trop, Cynthia TI INCIDENCE OF PLACEMENT AND REMOVAL OR REVISION OF TRANSVAGINAL MESH FOR PROLAPSE AND STRESS URINARY INCONTINENCE BEFORE AND AFTER THE 2011 FDA NOTIFICATION SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU) CY FEB 26-MAR 02, 2013 CL Las Vegas, NV SP Soc Urodynam & Female Urol (SUFU) C1 [Polland, Allison] Mt Sinai Med Ctr, New York, NY 10029 USA. [Meckel, Katherine] Columbia Univ, New York, NY USA. [Trop, Cynthia] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2013 VL 32 IS 2 BP 200 EP 200 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 093WG UT WOS:000315223200215 ER PT J AU Shen, C Kaelin, WG AF Shen, Chuan Kaelin, William G., Jr. TI The VHL/HIF axis in clear cell renal carcinoma SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Kidney cancer; von Hippel-Lindau; Hypoxia; Angiogenesis; VEGF ID HYPOXIA-INDUCIBLE FACTOR; EPIDERMAL-GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR GENE; PHASE-II TRIAL; OXYGEN-SENSING PATHWAY; MYELOID-LEUKEMIC-CELLS; PAS DOMAIN PROTEIN; FACTOR RECEPTOR; FACTOR-ALPHA AB Inactivation of the VHL tumor suppressor protein (pVHL) is a common event in clear cell renal carcinoma, which is the most common form of kidney cancer. pVHL performs many functions, including serving as the substrate recognition module of an ubiquitin ligase complex that targets the alpha subunits of the heterodimeric HIF transcription factor for proteasomal degradation. Deregulation of HIF2 alpha appears to be a driving force in pVHL-defective clear cell renal carcinomas. In contrast, genetic and functional studies suggest that HIFI a serves as a tumor suppressor and is a likely target of the 14q deletions that are characteristic of this tumor type. Drugs that inhibit HIF2 alpha, or its downstream targets such as VEGF, are in various stages of clinical testing. Indeed, clear cell renal carcinomas are exquisitely sensitive to VEGF deprivation and four VEGF inhibitors have now been approved for the treatment of this disease. (C) 2012 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 457, Boston, MA 02215 USA. EM William_kaelin@dfci.harvard.edu FU NIH; HHMI; Doris Duke Foundation FX Funding; NIH, HHMI, Doris Duke Foundation. NR 144 TC 90 Z9 93 U1 8 U2 23 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 2013 VL 23 IS 1 BP 18 EP 25 DI 10.1016/j.semcancer.2012.06.001 PG 8 WC Oncology SC Oncology GA 094CI UT WOS:000315240200004 PM 22705278 ER PT J AU Gunn, AJ Iqbal, SI Kalva, SP Walker, TG Ganguli, S Salazar, GM Oklu, R Wicky, S AF Gunn, Andrew J. Iqbal, Shams I. Kalva, Sanjeeva P. Walker, T. Gregory Ganguli, Suvranu Salazar, Gloria M. Oklu, Rahmi Wicky, Stephan TI Intravascular Ultrasound-Guided Inferior Vena Cava Filter Placement Using a Single-Puncture Technique in 99 Patients SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE IVC filter; intravascular ultrasound; deep vein thrombosis; pulmonary embolism ID INTENSIVE-CARE-UNIT; TRAUMA PATIENTS; PULMONARY-EMBOLISM; BEDSIDE INSERTION; MULTIPLE-TRAUMA; RENAL VEINS; CAVOGRAPHY; EXPERIENCE; PREVENTION; GUIDELINES AB Purpose: To assess the feasibility and safety of intravascular ultrasound (IVUS) to guide inferior vena cava (IVC) filter placement using a single venous puncture technique. Materials and Methods: Medical records of all patients who had IVC filters placed under IVUS guidance between January 1, 2005 and December 31, 2011 were retrospectively reviewed for pertinent history, results, and complications. All filters were placed using a single venous puncture technique. Results: Filters were successfully placed within the IVC in 94% of the patients with 6 malpositioned filters (4 in the iliac veins and 2 in the suprarenal IVC). Complications included groin hematoma (4%), deep venous thrombosis at the site of vascular access (2%), and filter tilt >15 degrees along the long axis of the IVC (2%). Conclusions: The IVUS-guided IVC filter placement using a single venous puncture technique is technically feasible and safe when compared to case series using a double venous puncture technique. C1 [Gunn, Andrew J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gunn, Andrew J.; Kalva, Sanjeeva P.; Walker, T. Gregory; Ganguli, Suvranu; Salazar, Gloria M.; Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Iqbal, Shams I.] Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. [Kalva, Sanjeeva P.; Walker, T. Gregory; Ganguli, Suvranu; Salazar, Gloria M.; Oklu, Rahmi; Wicky, Stephan] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM agunn@partners.org NR 22 TC 2 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD FEB PY 2013 VL 47 IS 2 BP 97 EP 101 DI 10.1177/1538574412473186 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 094SY UT WOS:000315285300003 PM 23315196 ER PT J AU Reisner, AT Heldt, T AF Reisner, Andrew T. Heldt, Thomas TI A computational model of hemorrhage and dehydration suggests a pathophysiological mechanism: Starling-mediated protein trapping SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE circulation; computer model; interstitial fluid; lymphatics; hemorrhage ID BLOOD-VOLUME; MATHEMATICAL-MODEL; UNCONTROLLED HEMORRHAGE; HEMODYNAMIC-RESPONSE; FLUID RESUSCITATION; PLASMA-VOLUME; TRAUMA DEATHS; RESTITUTION; SHOCK; EPIDEMIOLOGY AB Reisner AT, Heldt T. A computational model of hemorrhage and dehydration suggests a pathophysiological mechanism: Starling-mediated protein trapping. Am J Physiol Heart Circ Physiol 304: H620-H631, 2013. First published November 30, 2012; doi:10.1152/ajpheart.00621.2012.-We sought to understand the degree to which a single computational cardiovascular model could replicate the typical responses of healthy subjects through a breadth of blood loss patterns and whether such a model could illuminate the cause-effect relationships that underlie the observed responses. The model consisted of compartments for the upper body, lower body, viscera, and kidneys as well as a four-chambered heart and a pulmonary compartment. Transcapillary fluid flux was governed by Starling forces, whereas lymphatic flow was driven by hydrostatic tissue pressure and scaled by a lymphatic activation term. We adjusted parameters based on results from one protocol involving moderate continual blood loss in a canine model. Next, we simulated six additional protocols spanning euvolemic and dehydrated subjects and compared in silico behavior with in vivo hemodynamic responses and fluid shifts. The model was able to replicate group-averaged behavior (i.e., within 1 or 2 SEs) of the rate and quantity of vascular refill and the associated cardiac output during slow, moderate, and rapid ongoing blood losses, the restitution after the cessation of blood loss, and the absence of restitution in dehydrated subjects. The model suggested that the earlier phase of restitution, i.e., transcapillary fluid shifts, was antagonistic to the later phase of restitution, i.e., protein return via lymphatics. This phenomenon was termed "interstitial protein trapping." In conclusion, the model appears valid for a range of blood loss patterns and prehydration states. Further investigation into the in vivo relevance of interstitial protein trapping is justified. C1 [Reisner, Andrew T.] MIT, Div Hlth Sci & Technol, Boston, MA USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Reisner, Andrew T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Heldt, Thomas] MIT, Elect Res Lab, Computat Physiol & Clin Inference Grp, Cambridge, MA 02139 USA. RP Reisner, AT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM Areisner@partners.org NR 39 TC 0 Z9 0 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2013 VL 304 IS 4 BP H620 EP H631 DI 10.1152/ajpheart.00621.2012 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 092SE UT WOS:000315141500013 PM 23203962 ER PT J AU Krishnan, JA Lindenauer, PK Au, DH Carson, SS Lee, TA McBurnie, MA Naureckas, ET Vollmer, WM Mularski, RA AF Krishnan, Jerry A. Lindenauer, Peter K. Au, David H. Carson, Shannon S. Lee, Todd A. McBurnie, Mary Ann Naureckas, Edward T. Vollmer, William M. Mularski, Richard A. TI Stakeholder Priorities for Comparative Effectiveness Research in Chronic Obstructive Pulmonary Disease A Workshop Report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE health services research; research priorities; care coordination; stakeholders ID COPD AB Comparative effectiveness research (CER) is intended to address the expressed needs of patients, clinicians, and other stakeholders. Representatives of 54 stakeholder groups with an interest in chronic obstructive pulmonary disease (COPD) participated in workshops convened by the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period. Year 1 focused on chronic care and care coordination. Year 2 focused on acute care and transitions in care between healthcare settings. Discussions and provisional voting were conducted via teleconferences and e-mail exchanges before the workshop. Final prioritization votes occurred after in-person discussions at the workshop. We used a modified Delphi approach to facilitate discussions and consensus building. To more easily quantify preferences and to evaluate the internal consistency of rankings, the Analytic Hierarchy Process was incorporated in Year 2. Results of preworkshop and final workshop voting often differed, suggesting that prioritization efforts relying solely on requests for topics from stakeholder groups without in-person discussion may provide different research priorities. Research priorities varied across stakeholder groups, but generally focused on studies to evaluate different approaches to healthcare delivery (e.g., spirometry for diagnosis and treatment, integrated healthcare strategies during transitions in care) rather than head-to-head comparisons of medications. This research agenda may help to inform groups intending to respond to CER funding opportunities in COPD. The methodologies used, detailed in the online supplement, may also help to inform prioritization efforts for CER in other health conditions. C1 [Krishnan, Jerry A.; Lee, Todd A.] Univ Illinois, Chicago, IL 60612 USA. [Lindenauer, Peter K.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA USA. [Lindenauer, Peter K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, David H.] Univ Washington, Seattle, WA 98195 USA. [Carson, Shannon S.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. [McBurnie, Mary Ann; Vollmer, William M.; Mularski, Richard A.] Kaiser Permanente Ctr Hlth Res, Ctr Hlth Res, Portland, OR USA. [Naureckas, Edward T.] Univ Illinois, Sect Pulm & Crit Care, Chicago, IL 60612 USA. RP Krishnan, JA (reprint author), Univ Illinois, Hosp & Hlth Sci Syst, Med Ctr Adm Bldg,MC 973,914 S Wood St, Chicago, IL 60612 USA. EM jakris@uic.edu FU Agency for Healthcare Research and Quality [AHRQ R13 HS017894]; National Institutes of Health/National Heart, Lung, and Blood Institute [NIH/NHLBI RC2 HL1011618]; Health Services Research and Development, Department of Veterans Affairs FX Supported by Agency for Healthcare Research and Quality grant AHRQ R13 HS017894 and National Institutes of Health/National Heart, Lung, and Blood Institute grant NIH/NHLBI RC2 HL1011618. D.H.A. is supported through Health Services Research and Development, Department of Veterans Affairs. NR 16 TC 15 Z9 17 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2013 VL 187 IS 3 BP 320 EP 326 DI 10.1164/rccm.201206-0994WS PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 088TT UT WOS:000314860700014 PM 23155144 ER PT J AU Miller, YE Karoor, V Dempsey, EC AF Miller, York E. Karoor, Vijaya Dempsey, Edward C. TI Sleep-disordered Breathing, Hypoxemia, and Cancer Mortality SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID DISEASE; MECHANISM; APNEA C1 [Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado Denver, Aurora, CO USA. RP Miller, YE (reprint author), Denver Vet Affairs Med Ctr, Denver, CO USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2013 VL 187 IS 3 BP 330 EP 331 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 088TT UT WOS:000314860700021 PM 23378442 ER PT J AU Dording, CM LaRocca, RA Hails, KA Vitolo, OV Wisniewski, SR Balasubramani, GK Trivedi, M Fava, M Mischoulon, D AF Dording, Christina M. LaRocca, Rachel A. Hails, Katherine A. Vitolo, Ottavio V. Wisniewski, Stephen R. Balasubramani, Goundappa K. Trivedi, Madhukar Fava, Maurizio Mischoulon, David TI The effect of sildenafil on quality of life SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE major depressive disorder; sexual dysfunction; antidepressant; libido; sildenafil; quality of life ID INDUCED SEXUAL DYSFUNCTION; ERECTILE DYSFUNCTION; DOUBLE-BLIND; QUESTIONNAIRE; OUTPATIENTS; TRIAL AB BACKGROUND: Antidepressant-induced sexual dysfunction affects approximately 50% of patients taking antidepressants. Previous research has explored sildenafil's effectiveness in treating various forms of erectile dysfunction, but there is no research supporting sildenafil's use for improving the quality of life for patients with sexual dysfunction linked to antidepressant use. The authors of this article aimed to assess the improvements in quality of life in patients taking sildenafil to treat antidepressant-induced sexual dysfunction. METHODS: One hundred and two out of 2,239 male and female patients in the follow-up phase of the Sequenced Treatment Alternatives to Relieve Depression antidepressant trials who complained of sexual dysfunction were given sildenafil, 50 to 100 mg, as needed. After 12 months, we measured patients' change in libido, sexual drive, family relationships, overall well-being, satisfaction with treatment, and overall contentment with items on the 17-item Hamilton Depression Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, 30-item Inventory of Depressive Symptoms, and 12-item Short Form Health Survey. RESULTS: There was a significant association between sildenafil use and improvement in libido and sexual drive by month 6. There was no significant improvement in the quality-of-life scores we examined, but treatment satisfaction and overall contentment increased over time. CONCLUSIONS: Despite no direct association with sildenafil use and quality-of-life scores, sildenafil may be a beneficial treatment for antidepressant-induced sexual dysfunction. A double-blind, placebo-controlled study of sildenafil in antidepressant-induced sexual dysfunction is needed to further explore its potential benefits. C1 [Dording, Christina M.; LaRocca, Rachel A.; Hails, Katherine A.; Vitolo, Ottavio V.; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Balasubramani, Goundappa K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Trivedi, Madhukar] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM cdording@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860; Goundappa K, Balasubramani/0000-0001-7221-1825 FU Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions; Clintara; Covance; Covidien; Eli Lilly and Company; ElMindA; EnVivo Pharmaceuticals; Euthymics Bioscience; Forest Pharmaceuticals; Ganeden Biotech; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research and Development; Lichtwer Pharma; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis; Organon Pharmaceuticals; PamLab, LLC; Pfizer, Inc.; Pharmavite; Photothera; Roche Pharmaceuticals; RCT Logic; sanofi-aventis; Shire; Solvay Pharmaceutical; Synthelabo; Wyeth-Ayerst Laboratories; Clinical Investigator Training Program at Beth Israel Deaconess Medical Center, Harvard Medical School; Merck; Ibdi Ibrahim; Agency for Healthcare Research and Quality; Akzo (Organon Pharmaceuticals); Axon Advisors; Corcept Therapeutics; Cyberonics; Evotek; Fabre-Kramer Pharmaceuticals; Janssen Pharmaceutica; Libby; Lundbeck, Inc.; Meade Johnson; MedAvante; Medtronic; NARSAD; Naurex; Neuronetics; NIDA; NIMH; Otsuka Pharmaceuticals; Parke-Davis Pharmaceuticals; PgxHealth; Pharmacia Upjohn; Predix Pharmaceuticals; Rexahn Pharmaceuticals; Sepracor; Shire Development; Sierra; SK Life and Science; Solvay Pharmaceuticals; Takeda Pharmaceutical Company Limited; Tai Medical/Puretech Venture; Targacept; Transcept; Valient; VantagePoint; BrainCells Inc.; CeNeRx Bio Pharma; Clinical Trials Solutions, LLC; Clintara, LLC; ElMindA, Ltd.; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; NCCAM; Novartis AG; Pharmavite LLC; RCT Logic, LLC; Solvay Pharmaceuticals, Inc.; Bowman Family Foundation; FisherWallace; Nordic Naturals; NIMH/National Institutes of Health [N01MH90003] FX Dr. Dording has received research support from Abbott Laboratories, Alkermes, Inc., Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, Clintara, Covance, Covidien, Eli Lilly and Company, ElMindA, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson Pharmaceutical Research and Development, Lichtwer Pharma, Lorex Pharmaceuticals, National Alliance for Research on Schizophrenia and Depression (NARSAD), National Center for Complementary and Alternative Medicine (NCCAM), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), Novartis, Organon Pharmaceuticals, PamLab, LLC, Pfizer, Inc., Pharmavite, Photothera, Roche Pharmaceuticals, RCT Logic, sanofi-aventis, Shire, Solvay Pharmaceutical, Synthelabo, and Wyeth-Ayerst Laboratories; has served as an advisor or consultant to Takeda; and has been a speaker for Wyeth-Ayerst Laboratories. Dr. Vitolo receives grant or research support from the Clinical Investigator Training Program at Beth Israel Deaconess Medical Center, Harvard Medical School, funded in part by an unrestricted educational grant from Merck and Pfizer, Inc. Dr. Wisniewski is a consultant to Bristol-Myers Squibb, Case Western Reserve University, Cyberonic, Dey Pharmaceuticals, ImaRx Therapeutics, Organon Pharmaceuticals, Singapore Clinical Research Institute, and Venebio. Dr. Trivedi received research support from or has been a consultant or speaker for Abbott Laboratories, Ibdi Ibrahim, Agency for Healthcare Research and Quality, Akzo (Organon Pharmaceuticals), Alkermes, Inc., AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Corcept Therapeutics, Cyberonics, Eli Lilly and Company, Evotek, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research and Development, Libby, Lundbeck, Inc., Meade Johnson, MedAvante, Medtronic, Merck, NARSAD, Naurex, Neuronetics, NIDA, NIMH, Novartis, Otsuka Pharmaceuticals, PamLab, LLC, Parke-Davis Pharmaceuticals, Pfizer, Inc., PgxHealth, Pharmacia & Upjohn, Predix Pharmaceuticals, Rexahn Pharmaceuticals, Sepracor, Shire Development, Sierra, SK Life and Science, Solvay Pharmaceuticals, Takeda Pharmaceutical Company Limited, Tai Medical/Puretech Venture, Targacept, Transcept, Valient, VantagePoint, and Wyeth-Ayerst Laboratories. Dr. Fava receives research support from Abbott Laboratories, Alkermes, Inc., Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells Inc., Bristol-Myers Squibb, CeNeRx Bio Pharma, Cephalon, Clinical Trials Solutions, LLC, Clintara, LLC, Covance, Covidien, Eli Lilly and Company, ElMindA, Ltd., EnVivo Pharmaceuticals, Inc., Euthymics Bioscience, Inc., Forest Pharmaceuticals, Inc., Ganeden Biotech, Inc., GlaxoSmithKline, i3 Innovus/Ingenix, Icon Clinical Research, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIMH, NIDA, Novartis AG, Organon Pharmaceuticals, PamLab, LLC, Pfizer Inc., Pharmavite LLC, Photothera, RCT Logic, LLC, Roche Pharmaceuticals, sanofi-aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories; is an advisor or consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Alkermes, Inc., Amarin Pharma, Inc., Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc.; , BioMarin Pharmaceuticals, Inc., Biovail Corporation, BrainCells Inc., Bristol-Myers Squibb, CeNeRx Bio Pharma, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Inc., Compellis Pharmaceutics, Cypress Pharmaceutical, Inc., DiagnoSearch Life Sciences (P) Ltd., Dainippon Sumitomo Pharma Co. Inc., Dov Pharmaceuticals, Inc., Edgemont Pharmaceuticals, Inc., Eisai, Inc., Eli Lilly and Company, EnVivo Pharmaceuticals, Inc., ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, Inc., GenOmind, LLC, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenix, Janssen Pharmaceutica, Jazz Pharmaceuticals, Inc., Johnson & Johnson Pharmaceutical Research & Development, Knoll Pharmaceuticals Corp., Labopharm, Inc., Lorex Pharmaceuticals, Lundbeck, Inc., MedAvante, Inc., Merck, MSI Methylation Sciences, Inc., Naurex, Inc., Neuronetics, Inc., NextWave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Inc., Organon Pharmaceuticals, Otsuka Pharmaceuticals, PamLab, LLC, Pfizer, Inc., PharmaStar, Pharmavite LLC, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Inc., PsychoGenics, Psylin Neurosciences, Inc., Puretech Ventures, RCT Logic, LLC, Rexahn Pharmaceuticals, Inc., Ridge Diagnostics, Inc., Roche Pharmaceuticals, sanofi-aventis, Schering-Plough Corporation, Sepracor, Inc., Servier Laboratories, Solvay Pharmaceuticals, Inc., Somaxon Pharmaceuticals, Inc., Somerset Pharmaceuticals, Inc., Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Inc., Synthelabo, Takeda Pharmaceutical Company Limited, Tal Medical, Inc., Tetragenex Pharmaceuticals, Inc., Transcept Pharmaceuticals, Inc., TransForm Pharmaceuticals, Inc., and Vanda Pharmaceuticals, Inc.; is a speaker for or has been published by: Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, Inc., CME Institute/Physicians Postgraduate Press, Inc., Eli Lilly and Company, Forest Pharmaceuticals, Inc., GlaxoSmithKline, Imedex, LLC, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon Pharmaceuticals, Pfizer, Inc., PharmaStar, United BioSource Corp., and Wyeth-Ayerst Laboratories; has equity holdings with Compellis; has a patent for Sequential Parallel Comparison Design (SPCD) and a patent application for a combination of azapirones and bupropion in major depressive disorder, for research and licensing of SPCD with RCP Logic; and has a copyright for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. Dr. Mischoulon receives grant or research support from the Bowman Family Foundation, FisherWallace, and Nordic Naturals; is a speaker for MGH Psychiatry Academy; and received royalties from Lippincott Williams & Wilkins. Ms. LaRocca, Ms. Hails, and Dr. Balasubramani report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.; The initial STAR*D project was supported with federal funds from the NIMH/National Institutes of Health under contract N01MH90003 to the University of Texas Southwestern Medical Center, Dallas (PI: Dr. A.J. Rush). The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. The NIMH approved the design of the overall study and reviewed its conduct but performed no role in the collection, management, or interpretation of the data analyzed for this report or in the preparation, review, or approval of the manuscript. We appreciate the support of Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, Inc., and Wyeth for providing medications at no cost for the original STAR*D trial. None of these entities had a role in any part of the study (eg, design, execution, data collection, analysis, or interpretation of the data), nor in writing any report, including this one. NR 12 TC 4 Z9 4 U1 0 U2 2 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD FEB PY 2013 VL 25 IS 1 BP 3 EP 10 PG 8 WC Psychiatry SC Psychiatry GA 091UF UT WOS:000315074600002 PM 23376864 ER PT J AU Nyer, M Holt, DJ Pedrelli, P Fava, M Ameral, V Cassiello, CF Nock, MK Ross, M Hutchinson, D Farabaugh, A AF Nyer, Maren Holt, Daphne J. Pedrelli, Paola Fava, Maurizio Ameral, Victoria Cassiello, Clair F. Nock, Matthew K. Ross, Margaret Hutchinson, Dori Farabaugh, Amy TI Factors that distinguish college students with depressive symptoms with and without suicidal thoughts SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE suicide; depression; college students; anxiety; undergraduate; hopelessness ID IDEATION; HOPELESSNESS; QUESTIONNAIRE; PREVALENCE; PREDICTORS; BEHAVIOR; RISK AB BACKGROUND: Suicide among college students is a significant public health concern. Although suicidality is linked to depression, not all depressed college students experience suicidal ideation (SI). The primary aim of this study was to determine potential factors that may distinguish college students with depressive symptoms with and without SI. METHODS: A total of 287 undergraduate college students with substantial depressive symptoms (Beck Depression Inventory [BDI] total score >13) with and without SI were compared across psychiatric and functional outcome variables. Independent sample t tests were conducted for each outcome variable using the suicide item of the BDI as a dichotomous (ie, zero vs nonzero score) grouping variable. RESULTS: Relative to students with substantial depressive symptoms without SI, those with SI were more symptomatic overall, having significantly higher levels of depressive symptoms, hopelessness, and anxiety. However, contrary to our expectations, nonsuicidal and suicidal students did not differ on measures of everyday functioning (ie, cognitive and physical functioning and grade point average). CONCLUSIONS: Our findings suggest that SI among college students is associated with increased subjective distress but may not adversely impact physical or cognitive functioning or academic performance. C1 [Nyer, Maren; Holt, Daphne J.; Pedrelli, Paola; Fava, Maurizio; Ameral, Victoria; Cassiello, Clair F.; Farabaugh, Amy] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Ross, Margaret] Boston Univ, Student Hlth Serv, Boston, MA 02215 USA. [Hutchinson, Dori] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. RP Nyer, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org FU Harvard Medical School; Kaplen Fellowship; Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx Bio Pharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; ElMindA Ltd.; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; i3 Innovus/Ingenix; Icon Clinical Research; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; National Center for Complementary and Alternative Medicine; National Institute of Mental Health; National Institute on Drug Abuse; Novartis AG; Organon Pharmaceuticals; PamLab, LLC; Pfizer, Inc.; Pharmavite LLC; Photothera; RCT Logic, LLC; Roche Pharmaceuticals; sanofi-aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Jed Foundation FX Dr. Nyer receives grant or research support from Harvard Medical School and the Kaplen Fellowship. Dr. Fava receives research support from Abbott Laboratories, Alkermes, Inc., Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells Inc., Bristol-Myers Squibb, CeNeRx Bio Pharma, Cephalon, Clinical Trials Solutions, LLC, Clintara, LLC, Covance, Covidien, Eli Lilly and Company, ElMindA Ltd., EnVivo Pharmaceuticals, Inc., Euthymics Bioscience, Inc., Forest Pharmaceuticals, Inc., Ganeden Biotech, Inc., GlaxoSmithKline, i3 Innovus/Ingenix, Icon Clinical Research, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, National Center for Complementary and Alternative Medicine, National Institute of Mental Health, National Institute on Drug Abuse, Novartis AG, Organon Pharmaceuticals, PamLab, LLC, Pfizer, Inc., Pharmavite LLC, Photothera, RCT Logic, LLC, Roche Pharmaceuticals, sanofi-aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories; is an advisor or consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Alkermes, Inc., Amarin Pharma, Inc., Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc., BioMarin Pharmaceuticals, Inc., Biovail Corporation, Brain Cells Inc., Bristol-Myers Squibb, CeNeRx Bio Pharma, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Inc., Compellis Pharmaceutics, Cypress Pharmaceutical, Inc., DiagnoSearch Life Sciences (P) Ltd., Dainippon Sumitomo Pharma Co. Inc., Dov Pharmaceuticals, Inc., Edgemont Pharmaceuticals, Inc., Eisai, Inc., Eli Lilly and Company, En Vivo Pharmaceuticals, Inc., ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, Inc., GenOmind, LLC, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenix, Janssen Pharmaceutica, Jazz Pharmaceuticals, Inc., Johnson & Johnson Pharmaceutical Research & Development, Knoll Pharmaceuticals Corp., Labopharm Inc., Lorex Pharmaceuticals, Lundbeck Inc., MedAvante, Inc., Merck, MSI Methylation Sciences, Inc., Naurex, Inc., Neuronetics, Inc., Next Wave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Inc., Organon Pharmaceuticals, Otsuka Pharmaceuticals, PamLab, LLC, Pfizer, Inc., PharmaStar, Pharmavite LLC, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Inc., PsychoGenics, Psylin Neurosciences, Inc., Puretech Ventures, RCT Logic, LLC, Rexahn Pharmaceuticals, Inc., Ridge Diagnostics, Inc., Roche Pharmaceuticals, sanofi-aventis, Schering-Plough Corporation, Sepracor, Inc., Servier Laboratories, Solvay Pharmaceuticals, Inc., Somaxon Pharmaceuticals, Inc., Somerset Pharmaceuticals, Inc., Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Inc., Synthelabo, Takeda Pharmaceutical Company Limited, Tal Medical, Inc., Tetragenex Pharmaceuticals, Inc., Transcept Pharmaceuticals, Inc., Trans Form Pharmaceuticals, Inc., and Vanda Pharmaceuticals, Inc.; is a speaker for or has been published by: Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, Inc., CME Institute/Physicians Postgraduate Press, Inc., Eli Lilly and Company, Forest Pharmaceuticals, Inc., GlaxoSmithKline, Imedex, LLC, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon Pharmaceuticals, Pfizer, PharmaStar, United BioSource Corp.; , and Wyeth-Ayerst Laboratories; has equity holdings with Compellis; has a patent for Sequential Parallel Comparison Design (SPCD) and a patent application for a combination of azapirones and bupropion in major depressive disorder, for research and licensing of SPCD with RCP Logic; and has a copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. Drs. Holt, Pedrelli, Nock, Ross, Hutchinson, and Farabaugh, Ms. Ameral, and Ms. Cassiello report no financial relationships with any products are mentioned in this article or with manufacturers of competing products. This study was supported by a grant from The Jed Foundation. NR 33 TC 11 Z9 11 U1 2 U2 21 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD FEB PY 2013 VL 25 IS 1 BP 41 EP 49 PG 9 WC Psychiatry SC Psychiatry GA 091UF UT WOS:000315074600007 PM 23376869 ER PT J AU Wilcox, SR Brown, DFM Elmer, J AF Wilcox, Susan R. Brown, David F. M. Elmer, Jonathan TI Video Laryngoscopy Is a Valuable Adjunct in Emergency Airway Management but Is Not Sufficient as an Exclusive Method of Training Residents SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter ID TRACHEAL INTUBATIONS C1 [Wilcox, Susan R.; Brown, David F. M.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Wilcox, Susan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Elmer, Jonathan] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. RP Wilcox, SR (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. OI Wilcox, Susan/0000-0001-7477-7531 NR 5 TC 3 Z9 3 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD FEB PY 2013 VL 61 IS 2 BP 252 EP 253 DI 10.1016/j.annemergmed.2012.07.127 PG 2 WC Emergency Medicine SC Emergency Medicine GA 086FJ UT WOS:000314669200020 PM 23331650 ER PT J AU Pak, TR Roth, FP AF Pak, Theodore R. Roth, Frederick P. TI ChromoZoom: a flexible, fluid, web-based genome browser SO BIOINFORMATICS LA English DT Article ID DATABASE AB A: Current web-based genome browsers require repetitious user input to scroll over long distances, alter the drawing density of elements or zoom through multiple orders of magnitude. Generally, either the server or the client is responsible for the majority of data processing, resulting in either servers having to receive and handle data relevant only to one user, or clients redundantly processing widely viewed data. ChromoZoom pre-renders and caches general-use tracks into tiled images on the server and serves them in an interactive web interface with inertial scrolling and precise, fluent zooming via the mouse wheel or trackpad. Custom tracks in several formats can be rendered by client-side code alongside the pre-rendered tracks, minimizing server load because of user-specific rendering and eliminating the need to transmit private data. ChromoZoom thereby enables rapid and simultaneous exploration of curated, experimental and personal genomic datasets. C1 [Pak, Theodore R.; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Pak, Theodore R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. EM fritz.roth@utoronto.ca RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU National Institutes of Health [HG004233, HL107440]; Ontario Research Fund-Research Excellence Award; Canadian Institute for Advanced Research Fellowship; Canada Excellence Research Chair FX National Institutes of Health (HG004233, HL107440); Ontario Research Fund-Research Excellence Award; Canadian Institute for Advanced Research Fellowship; Canada Excellence Research Chair (to F.P.R.). NR 11 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD FEB 1 PY 2013 VL 29 IS 3 BP 384 EP 386 DI 10.1093/bioinformatics/bts695 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 089EI UT WOS:000314892000012 PM 23220575 ER PT J AU Yaseen, MA Sakadzic, S Wu, WC Becker, W Kasischke, KA Boas, DA AF Yaseen, Mohammad A. Sakadzic, Sava Wu, Weicheng Becker, Wolfgang Kasischke, Karl A. Boas, David A. TI In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; TIME-RESOLVED FLUORESCENCE; PYRIDINE-NUCLEOTIDES; CELLULAR-METABOLISM; INTRACELLULAR NADH; RESPONSE FUNCTION; LIVE TISSUE; REVEALS; BRAIN; CELLS AB Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism. (c) 2013 Optical Society of America C1 [Yaseen, Mohammad A.; Sakadzic, Sava; Wu, Weicheng; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Opt Div, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Becker, Wolfgang] Becker & Hickl GmbH, D-12277 Berlin, Germany. [Kasischke, Karl A.] Univ Ulm, Med Ctr, Dept Neurol, D-89075 Ulm, Germany. RP Yaseen, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Opt Div, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM dboas@nmr.mgh.harvard.edu FU NIH [R01-NS057476, P50-NS010828, P01-NS055104, R01-EB000790]; AHA [11SDG7600037] FX This work was supported by NIH R01-NS057476, P50-NS010828, and P01-NS055104, R01-EB000790 and AHA 11SDG7600037. We gratefully acknowledge Boston Electronics for their generous support with the TCSPC equipment and software. Dr. Becker has a financial interest in Becker & Hickl GmbH, which did not support this work. NR 53 TC 30 Z9 30 U1 2 U2 37 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD FEB 1 PY 2013 VL 4 IS 2 BP 307 EP 321 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 088AQ UT WOS:000314806600013 PM 23412419 ER PT J AU Chew, S Balasubramanian, R Chan, WM Kang, PB Andrews, C Webb, BD MacKinnon, SE Oystreck, DT Rankin, J Crawford, TO Geraghty, M Pomeroy, SL Crowley, WF Jabs, EW Hunter, DG Grant, PE Engle, EC AF Chew, Sheena Balasubramanian, Ravikumar Chan, Wai-Man Kang, Peter B. Andrews, Caroline Webb, Bryn D. MacKinnon, Sarah E. Oystreck, Darren T. Rankin, Jessica Crawford, Thomas O. Geraghty, Michael Pomeroy, Scott L. Crowley, William F., Jr. Jabs, Ethylin Wang Hunter, David G. Grant, Patricia E. Engle, Elizabeth C. TI A novel syndrome caused by the E410K amino acid substitution in the neuronal beta-tubulin isotype 3 SO BRAIN LA English DT Article DE Kallmann syndrome; cyclic vomiting; peripheral neuropathy; CFEOM; TUBB3 ID CYCLIC VOMITING SYNDROME; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; MOEBIUS SYNDROME; PERIPHERAL NEUROPATHY; KALLMANN-SYNDROME; TUBB3 MUTATIONS; GNRH DEFICIENCY; DISEASE-MODEL; MIGRATION; SEQUENCE AB Missense mutations in TUBB3, the gene that encodes the neuronal-specific protein beta-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of the extraocular muscles, a form of complex congenital strabismus characterized by cranial nerve misguidance. One of the eight TUBB3 mutations reported to cause congenital fibrosis of the extraocular muscles, c.1228G>A results in a TUBB3 E410K amino acid substitution that directly alters a kinesin motor protein binding site. We report the detailed phenotypes of eight unrelated individuals who harbour this de novo mutation, and thus define the 'TUBB3 E410K syndrome'. Individuals harbouring this mutation were previously reported to have congenital fibrosis of the extraocular muscles, facial weakness, developmental delay and possible peripheral neuropathy. We now confirm by electrophysiology that a progressive sensorimotor polyneuropathy does indeed segregate with the mutation, and expand the TUBB3 E410K phenotype to include Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), stereotyped midface hypoplasia, intellectual disabilities and, in some cases, vocal cord paralysis, tracheomalacia and cyclic vomiting. Neuroimaging reveals a thin corpus callosum and anterior commissure, and hypoplastic to absent olfactory sulci, olfactory bulbs and oculomotor and facial nerves, which support underlying abnormalities in axon guidance and maintenance. Thus, the E410K substitution defines a new genetic aetiology for Moebius syndrome, Kallmann syndrome and cyclic vomiting. Moreover, the c.1228G>A mutation was absent in DNA from similar to 600 individuals who had either Kallmann syndrome or isolated or syndromic ocular and/or facial dysmotility disorders, but who did not have the combined features of the TUBB3 E410K syndrome, highlighting the specificity of this phenotype-genotype correlation. The definition of the TUBB3 E410K syndrome will allow clinicians to identify affected individuals and predict the mutation based on clinical features alone. C1 [Chew, Sheena; Chan, Wai-Man; Kang, Peter B.; Andrews, Caroline; Rankin, Jessica; Pomeroy, Scott L.; Engle, Elizabeth C.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chew, Sheena; Chan, Wai-Man; Andrews, Caroline; Pomeroy, Scott L.; Engle, Elizabeth C.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Chew, Sheena; Kang, Peter B.; Andrews, Caroline; Pomeroy, Scott L.; Engle, Elizabeth C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Chew, Sheena; Rankin, Jessica] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chew, Sheena; Chan, Wai-Man; Andrews, Caroline; Engle, Elizabeth C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Balasubramanian, Ravikumar; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Balasubramanian, Ravikumar; Crowley, William F., Jr.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Balasubramanian, Ravikumar; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chan, Wai-Man; Andrews, Caroline; Engle, Elizabeth C.] Boston Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Webb, Bryn D.; Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Webb, Bryn D.; Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [MacKinnon, Sarah E.; Oystreck, Darren T.; Hunter, David G.; Engle, Elizabeth C.] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Crawford, Thomas O.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Geraghty, Michael] Univ Ottawa, Childrens Hosp Eastern Ontario, Dept Paediat, Ottawa, ON K1N 6N5, Canada. [Pomeroy, Scott L.; Engle, Elizabeth C.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Grant, Patricia E.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Engle, Elizabeth C.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Engle, Elizabeth C.] Boston Childrens Hosp, Dept Med Genet, Boston, MA 02115 USA. RP Engle, EC (reprint author), Boston Childrens Hosp, CLS14074,300 Longwood Ave, Boston, MA 02115 USA. EM Elizabeth.engle@childrens.harvard.edu FU National Eye Institute of the National Institutes of Health [R01EY12498]; Boston Children's Hospital Intellectual and Developmental Disabilities Research Centre [HD018655]; National Institute of Child Health & Human Development of the National Institutes of Health [U54 HD28138, T32 HD07396]; Children's Hospital Ophthalmology Foundation; Moebius Syndrome Foundation; HHMI Medical Fellowship; Harvard Medical School FX National Eye Institute of the National Institutes of Health [R01EY12498 to E.C.E.]; the Boston Children's Hospital Intellectual and Developmental Disabilities Research Centre [HD018655 to S.L.P., E.C.E.]; the National Institute of Child Health & Human Development of the National Institutes of Health [U54 HD28138 and T32 HD07396 to W.F.C.]; Children's Hospital Ophthalmology Foundation [to E.C.E., D.G.H.]; the Moebius Syndrome Foundation [to E.C.E.]. S.C is funded by the HHMI Medical Fellowship and Harvard Medical School. E.C.E. is a Howard Hughes Medical Institute Investigator. NR 47 TC 27 Z9 30 U1 0 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 2013 VL 136 BP 522 EP 535 DI 10.1093/brain/aws345 PN 2 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 090QX UT WOS:000314995200021 PM 23378218 ER PT J AU Pitman, MB AF Pitman, Martha Bishop TI Pancreatic cyst fluid triage A Critical Component of the Preoperative Evaluation of Pancreatic Cysts SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID PAPILLARY-MUCINOUS NEOPLASMS; ENDOSCOPIC ULTRASOUND; MOLECULAR ANALYSIS; ADDS VALUE; DIAGNOSIS; LESIONS; MANAGEMENT; CYTOLOGY; MALIGNANCY; ACCURATE C1 Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pitman, MB (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02115 USA. EM mpitman@partners.org NR 40 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD FEB PY 2013 VL 121 IS 2 BP 57 EP 60 DI 10.1002/cncy.21227 PG 4 WC Oncology; Pathology SC Oncology; Pathology GA 090NQ UT WOS:000314986300002 PM 22961913 ER PT J AU Kulu, Y Kawasaki, H Donahue, JM Kasuya, H Cusack, JC Choi, EW Kuruppu, DK Fuchs, BC Tanabe, KK AF Kulu, Y. Kawasaki, H. Donahue, J. M. Kasuya, H. Cusack, J. C. Choi, E. W. Kuruppu, D. K. Fuchs, B. C. Tanabe, K. K. TI Concurrent chemotherapy inhibits herpes simplex virus-1 replication and oncolysis SO CANCER GENE THERAPY LA English DT Article DE Herpes simplex virus; oncolytic HSV; viral oncolysis; combination therapy; chemotherapeutics ID NF-KAPPA-B; VIRAL RIBONUCLEOTIDE REDUCTASE; DIFFUSE LIVER METASTASES; DOUBLE-STRANDED-RNA; CELL LUNG-CANCER; COLORECTAL-CANCER; MALIGNANT GLIOMA; COLON-CARCINOMA; PHASE I/II; INDUCIBLE CHEMORESISTANCE AB Herpes simplex virus-1 (HSV-1) replication in cancer cells leads to their destruction (viral oncolysis) and has been under investigation as an experimental cancer therapy in clinical trials as single agents, and as combinations with chemotherapy. Cellular responses to chemotherapy modulate viral replication, but these interactions are poorly understood. To investigate the effect of chemotherapy on HSV-1 oncolysis, viral replication in cells exposed to 5-fluorouracil (5-FU), irinotecan (CPT-11), methotrexate (MTX) or a cytokine (tumor necrosis factor-alpha (TNF-alpha)) was examined. Exposure of colon and pancreatic cancer ceIIS to 5-FU, CPT-11 or MTX in vitro significantly antagonizes both HSV-1 replication and lytic oncolysis. Nuclear factor-kappa B (NF-kappa B) activation is required for efficient viral replication, and experimental inhibition of this response with an I kappa B alpha donninant-negative repressor significantly antagonizes HSV-1 replication. Nonetheless, cells exposed to 5-FU, CPT-11, TNF-alpha or HSV-1 activate NF-kappa B. Cells exposed to MTX do not activate NF-kappa B, suggesting a possible role for NF-kappa B inhibition in the decreased viral replication observed following exposure to MTX. The role of eukaryotic initiation factor 2 alpha (eIF-2 alpha) dephosphorylation was examined; HSV-1-mediated eIF-2 alpha dephosphorylation proceeds normally in HT29 cells exposed to 5-FU, CPT-11 or MTX. This report demonstrates that cellular responses to chemotherapeutic agents provide an unfavorable environment for HSV-1-mediated oncolysis, and these observations are relevant to the design of both preclinical and clinical studies of HSV-1 oncolysis. Cancer Gene Therapy (2013) 20, 133-140; doi:10.1038/cgt.2012.97; published online 25 January 2013 C1 [Tanabe, K. K.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. EM KTanabe@partners.org RI Kasuya, hideki/I-7278-2014 FU NIH [CA64454, CA76183, DK43352, CA71345, CA077278]; DFG [KU 1989/1-1] FX This work is supported by NIH Grants CA64454 and CA76183 (KK Tanabe), DK43352 (core facilities), CA71345 (JM Donahue) and CA077278 (JC Cusack) and DFG Grant KU 1989/1-1 (YKulu). NR 65 TC 3 Z9 3 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD FEB PY 2013 VL 20 IS 2 BP 133 EP 140 DI 10.1038/cgt.2012.97 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 091RV UT WOS:000315068400011 PM 23348635 ER PT J AU Marais, R Sellers, W Livingston, D Mihich, E AF Marais, Richard Sellers, William Livingston, David Mihich, Enrico TI Twenty-fourth Annual Pezcoller Symposium: Molecular Basis for Resistance to Targeted Agents SO CANCER RESEARCH LA English DT Editorial Material AB The mechanisms of genetically determined mechanisms of resistance to several target drugs were discussed in breast cancer, melanoma, colorectal and prostate cancers, chronic myelogenous leukemia, small cell lung cancer, and medulloblastoma. In each case, heterogeneity of mechanisms was emphasized. In melanoma, therapeutic interference with the effects of BRAF mutations was repeatedly discussed. It was also reported that anti-CTLA4 antibodies provided the first treatment improving survival of patients with stage IV melanoma. Epithelial-mesenchymal transition (EMT) was introduced as a mechanism of resistance, particularly in lung and pancreatic cancer, where the role of microenvironment factors was also indicated. In colorectal and prostate cancers, the use of liquid biopsies, namely, measurements of tumor nucleic acid in blood, were indicated as a way to obtain whole-tumor assessment instead of the partial assessment obtainable with traditional biopsies. Knowledge of the mechanisms of drug action and resistance was stressed to be essential for the design of new agents and combination of agents aimed at increasing antitumor effectiveness and overcoming resistance. Cancer Res; 73(3); 1046-9. (C) 2012 AACR. C1 [Marais, Richard] Paterson Inst Canc Res, Manchester M20 9BX, Lancs, England. [Sellers, William] Novartis Inst Biomed Res, Cambridge, England. [Livingston, David; Mihich, Enrico] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mihich, E (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM enrico_mihich@dfci.harvard.edu OI Marais, Richard/0000-0001-7484-4183 NR 0 TC 4 Z9 4 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2013 VL 73 IS 3 BP 1046 EP 1049 DI 10.1158/0008-5472.CAN-12-3236 PG 4 WC Oncology SC Oncology GA 091DD UT WOS:000315028300002 PM 23222297 ER PT J AU Chau, NG Haddad, RI AF Chau, Nicole G. Haddad, Robert I. TI Vandetanib for the Treatment of Medullary Thyroid Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT-TUMORS; PHASE-II; KINASE INHIBITORS; ZD6474; MUTATIONS AB Vandetanib (ZD6474, Caprelsa, AstraZeneca), an oral small-molecule tyrosine kinase inhibitor (TKI) that targets the rearranged during transfection receptor (RET), VEGF receptor (VEGFR2-3), and EGF receptor (EGFR), is the first systemic therapy approved by the U. S. Food and Drug Administration (FDA) for the treatment of symptomatic or progressive advanced medullary thyroid cancer (MTC). In a randomized phase III trial of patients with unresectable, locally advanced, or metastatic MTC, vandetanib improved progression-free survival compared with placebo [HR, 0.46; 95% confidence interval (CI), 0.31-0.69; P < 0.001]. However, the benefits in delaying disease progression need to be balanced against the associated and potentially serious toxicities, including diarrhea, hypertension, and QTc prolongation. Here, we review the clinical development of vandetanib leading to its integration into the current treatment paradigm and highlight the ongoing and future challenges in TKI use in MTC. Clin Cancer Res; 19(3); 524-9. (C) 2012 AACR. C1 [Chau, Nicole G.; Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Haddad, RI (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW430, Boston, MA 02215 USA. EM robert_haddad@dfci.harvard.edu FU Astra Zeneca FX R.I. Haddad has a commercial research grant from Astra Zeneca and is a consultant/advisory board member for Exelixis. No potential conflicts of interest were disclosed by N.G. Chau. NR 25 TC 20 Z9 21 U1 0 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2013 VL 19 IS 3 BP 524 EP 529 DI 10.1158/1078-0432.CCR-12-2353 PG 6 WC Oncology SC Oncology GA 088UQ UT WOS:000314863000004 PM 23231950 ER PT J AU Jiang, XF Zhou, J Giobbie-Hurder, A Wargo, J Hodi, FS AF Jiang, Xiaofeng Zhou, Jun Giobbie-Hurder, Anita Wargo, Jennifer Hodi, F. Stephen TI The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC MELANOMA; B7-H1 EXPRESSION; ACQUIRED-RESISTANCE; RAF INHIBITION; CANCER; PATHWAY; KINASE; BRAF(V600E); IMMUNORESISTANCE; VEMURAFENIB AB Purpose: Selective BRAF inhibition (BRAFi) provides a paradigm shift for melanoma treatment. The duration of benefit is typically limited before resistance develops. Interest remains in combining targeted and immune therapies to overcome resistance and improve durability of clinical benefit. One mechanism of evading immune destruction is programmed death-1-ligand 1 (PD-L1) expression by tumors that results in potent antitumor immune suppression. Experimental Design: BRAFi-resistant melanoma cells were examined for changes in PD-L1 expression by immunoblot and flow cytometry. Signaling pathways involved in altering PD-L1 expression were examined. Strategies to maximize the effect of the BRAFi therapy were studied including MEKi, MEKi combinations, and additional pathways including phosphoinositide-3 kinase (PI3K). Results: Melanoma cells resistant to BRAFi exhibit increased MAPK signaling and promotion of PD-L1 expression. PD-L1 expression is transcriptionally modulated by c-Jun and augmented by STAT3. MEK inhibition (MEKi) regains downregulation of MAPK signaling and suppresses the production of PD-L1. MEKi in melanoma cells shows dual therapeutic effects with simultaneous suppression of PD-L1 expression and induction of apoptosis. By combining MEKi with BRAFi, an additive effect on the inhibition of PD-L1 expression results. Conclusions: We report a novel mechanism that suppresses preexisting immune responses in patients with melanoma receiving BRAFi therapy. BRAFi resistance leads to increased expression of PD-L1 in melanoma cells, mediated by c-Jun and STAT3. MEKi may be feasible to counteract BRAFi resistance of MAPK reactivation and also for the additive effect of PD-L1 suppression. Potential therapeutic benefits of combining targeted inhibitors and immune modulation to improve patient outcomes should be investigated. Clin Cancer Res; 19(3); 598-609. (C) 2012 AACR. C1 [Jiang, Xiaofeng; Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wargo, Jennifer] Harvard Univ, Sch Med, Boston, MA USA. [Jiang, Xiaofeng; Zhou, Jun; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Dis Ctr, Boston, MA USA. [Zhou, Jun; Giobbie-Hurder, Anita; Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02215 USA. [Wargo, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU Sharon Crowley Martin Memorial Fund for Melanoma Research; Malcolm and Emily Mac Naught Fund for Melanoma Research at Dana-Farber Cancer Institute FX This work was supported in part by the Sharon Crowley Martin Memorial Fund for Melanoma Research (F. S. Hodi) and Malcolm and Emily Mac Naught Fund for Melanoma Research (F. S. Hodi) at Dana-Farber Cancer Institute. NR 46 TC 112 Z9 114 U1 3 U2 25 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2013 VL 19 IS 3 BP 598 EP 609 DI 10.1158/1078-0432.CCR-12-2731 PG 12 WC Oncology SC Oncology GA 088UQ UT WOS:000314863000012 PM 23095323 ER PT J AU Dogliotti, A Paolasso, E Giugliano, RP AF Dogliotti, Ariel Paolasso, Ernesto Giugliano, Robert P. TI Novel Oral Anticoagulants in Atrial Fibrillation: A Meta-analysis of Large, Randomized, Controlled Trials vs Warfarin SO CLINICAL CARDIOLOGY LA English DT Review ID STROKE PREVENTION; ELDERLY-PATIENTS; CLINICAL-TRIALS; DABIGATRAN; THERAPY; XIMELAGATRAN; RIVAROXABAN; QUALITY; RISK AB Background: Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings. Hypothesis: Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism. Methods: Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous). Results: In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.690.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug classoutcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001). Conclusions: Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes. Ernesto Paolasso, MD, is a national lead investigator for a clinical trial sponsored by Daiichi-Sankyo investigating a novel oral anticoagulant. Robert Giugliano, MD, SM, is a member of the TIMI Study Group, which has received research grant support from Johnson & Johnson and from Daiichi-Sankyo related to clinical trials of anticoagulants. Dr. Giugliano has received honoraria for consultation/lectures from Bristol-Myers Squibb, Daiichi-Sankyo, Johnson & Johnson, and Sanofi-Aventis. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Dogliotti, Ariel] Orono Grp, Clin Epidemiol & Stat Unit, Rosario, Santa Fe, Argentina. [Paolasso, Ernesto] Inst Invest Clin, Rosario, Santa Fe, Argentina. [Dogliotti, Ariel; Paolasso, Ernesto] Inst Cardiovasc Rosario, Rosario, Santa Fe, Argentina. [Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Daiichi-Sankyo; Johnson Johnson FX Ernesto Paolasso, MD, is a national lead investigator for a clinical trial sponsored by Daiichi-Sankyo investigating a novel oral anticoagulant. Robert Giugliano, MD, SM, is a member of the TIMI Study Group, which has received research grant support from Johnson & Johnson and from Daiichi-Sankyo related to clinical trials of anticoagulants. Dr. Giugliano has received honoraria for consultation/lectures from Bristol-Myers Squibb, Daiichi-Sankyo, Johnson & Johnson, and Sanofi-Aventis. NR 28 TC 35 Z9 38 U1 0 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD FEB PY 2013 VL 36 IS 2 BP 61 EP 67 DI 10.1002/clc.22081 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 090KA UT WOS:000314976700001 PM 23338902 ER PT J AU O'Hare, AM Vig, EK Hebert, PL AF O'Hare, Ann M. Vig, Elizabeth K. Hebert, Paul L. TI Initiation of Dialysis at Higher Levels of Estimated GFR and Subsequent Withdrawal SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID STAGE RENAL-DISEASE; LONG-TERM DIALYSIS; UNITED-STATES; ELDERLY-PATIENTS; KIDNEY-FUNCTION; OLDER-ADULTS; END; LIFE; DISCONTINUATION; INTENSITY C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP O'Hare, AM (reprint author), VA Med Ctr, 1160 S Columbian Way, Seattle, WA 98108 USA. EM ann.ohare@va.gov NR 29 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD FEB PY 2013 VL 8 IS 2 BP 179 EP 181 DI 10.2215/CJN.12841212 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 083TT UT WOS:000314488800003 PM 23349332 ER PT J AU Alge, JL Karakala, N Neely, BA Janech, MG Tomlin, JA Chawla, LS Shaw, AD Arthur, JM AF Alge, Joseph L. Karakala, Nithin Neely, Benjamin A. Janech, Michael G. Tomlin, James A. Chawla, Lakhmir S. Shaw, Andrew D. Arthur, John M. CA SAKInet Investigators TI Urinary Angiotensinogen and Risk of Severe AKI SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; ADULT CARDIAC-SURGERY; POOR OUTCOMES; OBSERVATIONAL COHORT; STATISTICAL-MODEL; CYSTATIN-C; BIOMARKERS; SYSTEM AB Background Biomarkers of AKI that can predict which patients will develop severe renal disease at the time of diagnosis will facilitate timely intervention in populations at risk of adverse outcomes. Design, setting, participants, & measurements Liquid chromatography/tandem mass spectrometry was used to identify 30 potential prognostic urinary biomarkers of severe AKI in a group of patients that developed AKI after cardiac surgery. Angiotensinogen had the best discriminative characteristics. Urinary angiotensinogen was subsequently measured by ELISA and its prognostic predictive power was verified in 97 patients who underwent cardiac surgery between August 1, 2008 and October 6, 2011. Results The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI, Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy, discharge >7 days from sample collection, and composite outcomes of AKIN stage 2 or 3, AKIN stage 3 or death, and renal replacement therapy or death. The prognostic predictive power of uAnCR was improved when only patients classified as AKIN stage 1 at the time of urine sample collection (n=79) were used in the analysis, among whom it predicted development of stage 3 AKI or death with an area under the curve of 0.81. Finally, category free net reclassification improvement showed that the addition of uAnCR to a clinical model to predict worsening of AM improved the predictive power. Conclusions Elevated uAnCR is associated with adverse outcomes inpatients with AKI. These data are the first to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI after cardiac surgery. Clin J Am Soc Nephrol 8: 184-193, 2013. doi: 10.2215/CJN.06280612 C1 [Alge, Joseph L.; Karakala, Nithin; Neely, Benjamin A.; Janech, Michael G.; Arthur, John M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Karakala, Nithin; Janech, Michael G.; Arthur, John M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Tomlin, James A.] Univ Tennessee, Coll Med, Chattanooga, TN USA. [Chawla, Lakhmir S.] George Washington Univ, Washington, DC USA. [Shaw, Andrew D.] Duke Univ, Durham, NC USA. [Shaw, Andrew D.] Durham Vet Affairs Med Ctr, Durham, NC USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM arthurj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811; Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066 FU National Institutes of Health [R01 DK080234, UL1 RR029882]; Department of Veterans Affairs; Nephcure Foundation FX This study was supported by the National Institutes of Health (Grants R01 DK080234 and UL1 RR029882) and by a Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. M.J. was supported by the Nephcure Foundation as a young investigator. The contents do not necessarily represent the views of the Department of Veterans Affairs or the US Government. NR 36 TC 24 Z9 25 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD FEB PY 2013 VL 8 IS 2 BP 184 EP 193 DI 10.2215/CJN.06280612 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 083TT UT WOS:000314488800005 PM 23143504 ER PT J AU Johansen, KL Kaysen, GA Dalrymple, LS Grimes, BA Glidden, DV Anand, S Chertow, GM AF Johansen, Kirsten L. Kaysen, George A. Dalrymple, Lorien S. Grimes, Barbara A. Glidden, David V. Anand, Shuchi Chertow, Glenn M. TI Association of Physical Activity with Survival among Ambulatory Patients on Dialysis: The Comprehensive Dialysis Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; DOSE-RESPONSE; MORTALITY; METAANALYSIS; COHORT; HEMODIALYSIS AB Background and objectives Despite high mortality and low levels of physical activity (PA) among patients starting dialysis, the link between low PA and mortality has not been carefully evaluated. Design, setting, participants, & measurements The Comprehensive Dialysis Study was a prospective cohort study that enrolled patients who started dialysis between June 2005 and June 2007 in a random sample of dialysis facilities in the United States. The Human Activity Profile (HAP) was administered to estimate PA among 1554 ambulatory enrolled patients in the Comprehensive Dialysis Study. Patients were followed until death or September 30, 2009, and the major outcome was all-cause mortality. Results The average age was 59.8 (14.2) years; 55% of participants were male, 28% were black, and 56% had diabetes mellitus. The majority (57.3%) had low fitness estimated from the HAP score. The median follow-up was 2.6 (interquartile range, 2.2-3.1) years. The association between PA and mortality was linear across the range of scores (1-94). After multivariable adjustment, lower adjusted activity score on the HAP was associated with higher mortality (hazard ratio, 1.30; 95% confidence interval, 1.23-1.39 per 10 points). Patients in the lowest level of fitness experienced a 3.5-fold (95% confidence interval, 2.54-4.89) increase in risk of death compared with those with average or above fitness. Conclusions Low levels of PA are strongly associated with mortality among patients new to dialysis. Interventions aimed to preserve or enhance PA should be prospectively tested. Clin J Am Soc Nephrol 8: 248-253, 2013. doi: 10.2215/CJN.08560812 C1 [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Kaysen, George A.; Dalrymple, Lorien S.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. [Grimes, Barbara A.; Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Anand, Shuchi; Chertow, Glenn M.] Stanford Univ, Div Nephrol, Stanford, CA 94305 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM Kirsten.johansen@ucsf.edu FU National Institutes of Health [N01-DK-1-2450, N01-DK-7-0005]; Abbott Laboratories Inc FX This study was supported by the National Institutes of Health (Contracts N01-DK-1-2450 to G.M.C. and N01-DK-7-0005 to K.L.J.). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.; K.L.J. has received grant support from Abbott Laboratories Inc and has served on Amgen's National Nephrology Advisory Board. NR 21 TC 26 Z9 27 U1 2 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD FEB PY 2013 VL 8 IS 2 BP 248 EP 253 DI 10.2215/CJN.08560812 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 083TT UT WOS:000314488800013 PM 23124787 ER PT J AU Soscia, SJ Fitzgerald, ML AF Soscia, Stephanie J. Fitzgerald, Michael L. TI The ABCA7 transporter, brain lipids and Alzheimer's disease SO CLINICAL LIPIDOLOGY LA English DT Review DE ABCAI; ABCA7; Alzheimer's disease; amyloid-beta; ApoE; ApoJ; brain; cholesterol homeostasis; genome-wide association study; lipid ID AMYLOID-BETA-PEPTIDE; GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; HIGH-DENSITY-LIPOPROTEIN; TRANSGENIC MOUSE MODEL; APOLIPOPROTEIN-E; A-BETA; CHOLESTEROL EFFLUX; III HYPERLIPOPROTEINEMIA; PROTEOLYTIC DEGRADATION AB ABCA7 is part of the ABCA superfamily of cholesterol and phospholipid transporters that move lipids and other molecules across membranes. The ABCA7 locus was one of four loci implicated in Alzheimer's disease (AD) susceptibility in a recent genome-wide association study. It is also one of three loci involved in both lipid homeostasis and increased risk for AD. The link between AD and altered brain lipid metabolism is reviewed here, with particular emphasis on the roles of ApoE, ApoJ and ABCA7. Advances in genome-wide studies have allowed researchers to explore the relationships between common sequence variations and disease predisposition. Investigating a link between the biological function of genetic variants and underlying disease pathology may be key to understanding AD cause, progression and treatment. C1 [Soscia, Stephanie J.; Fitzgerald, Michael L.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Soscia, SJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM ssoscia@gmail.com NR 138 TC 1 Z9 1 U1 1 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD FEB PY 2013 VL 8 IS 1 BP 97 EP 108 DI 10.2217/CLP.12.91 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 087VP UT WOS:000314792600016 ER PT J AU Ferris, M Norwood, V Radeva, M Gassman, JJ Al-Uzri, A Askenazi, D Matoo, T Pinsk, M Sharma, A Smoyer, W Stults, J Vyas, S Weiss, R Gipson, D Kaskel, F Friedman, A Moxey-Mims, M Trachtman, H AF Ferris, Maria Norwood, Victoria Radeva, Milena Gassman, Jennifer J. Al-Uzri, Amira Askenazi, David Matoo, Tej Pinsk, Maury Sharma, Amita Smoyer, William Stults, Jenna Vyas, Shefali Weiss, Robert Gipson, Debbie Kaskel, Frederick Friedman, Aaron Moxey-Mims, Marva Trachtman, Howard TI Patient Recruitment into a Multicenter Randomized Clinical Trial for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT) SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE clinical trials; kidney; nephrology; pediatrics ID RARE DISEASES; ENROLLMENT; CHILDREN AB We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 +/- 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 +/- 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. Clin Trans Sci 2013; Volume 6: 1320 C1 [Ferris, Maria] Univ N Carolina, Chapel Hill, NC USA. [Norwood, Victoria] Univ Virginia, Charlottesville, VA USA. [Radeva, Milena; Gassman, Jennifer J.] Cleveland Clin, Cleveland, OH 44106 USA. [Al-Uzri, Amira] Doernbecher Childrens Hosp, Portland, OR USA. [Askenazi, David] Univ Alabama Birmingham, Birmingham, AL USA. [Matoo, Tej] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Pinsk, Maury] Univ Alberta, Edmonton, AB, Canada. [Sharma, Amita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smoyer, William] Nationwide Childrens Hosp, Columbus, OH USA. [Stults, Jenna] Seattle Childrens Hosp, Seattle, WA USA. [Vyas, Shefali] St Barnabas Hosp, Livingston, NJ USA. [Weiss, Robert] New York Med Coll, Valhalla, NY 10595 USA. [Gipson, Debbie] Univ Michigan, Ann Arbor, MI 48109 USA. [Kaskel, Frederick] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Friedman, Aaron] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD USA. [Trachtman, Howard] NYU Langone Med Ctr, New York, NY USA. RP Trachtman, H (reprint author), NYU Langone Med Ctr, New York, NY USA. EM howard.trachtman@nyumc.org OI Pinsk, Maury/0000-0001-7668-665X; Trachtman, Howard/0000-0001-7447-9489 FU NIH-NIDDK [U01-DK063385, DK063490, DK063455, DK063549]; National Center for Research Resources: University of North Carolina [UL1 RR025747]; National Center for Research Resources: University of Michigan [UL1 RR0249860]; National Center for Research Resources: Harvard University [UL1 RR05758]; National Center for Research Resources: Albert Einstein College of Medicine [UL1 RR025750]; National Center for Research Resources: Medical University of South Carolina [UL1 RR029882] FX This study was sponsored by the NIH-NIDDK Grants U01-DK063385, DK063490, DK063455, and DK063549. In addition, the trial was supported by the following Clinical and Translational Science Awards from the National Center for Research Resources: University of North Carolina (UL1 RR025747), University of Michigan (UL1 RR0249860), Harvard University (UL1 RR05758), Albert Einstein College of Medicine (UL1 RR025750), and Medical University of South Carolina (UL1 RR029882). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Th e authors thank Edward Iglesia for his assistance in preparing Figure 2. NR 21 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD FEB PY 2013 VL 6 IS 1 BP 13 EP 20 DI 10.1111/cts.12003 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 089OK UT WOS:000314919700007 PM 23399084 ER PT J AU Sharon, VR Armstrong, AW On, SCJ Ibrahimi, OA Eisen, DB AF Sharon, Victoria R. Armstrong, April W. On, Shelbi C. Jim Ibrahimi, Omar A. Eisen, Daniel B. TI Separate- Versus Same-Day Preoperative Consultation in Dermatologic Surgery: A Patient-Centered Investigation in an Academic Practice SO DERMATOLOGIC SURGERY LA English DT Article ID MOHS MICROGRAPHIC SURGERY; CUTANEOUS SURGERY; WARFARIN; STROKE AB Background Little is known about patient preferences for preoperative consultation in dermatologic surgery. Objective To determine patient preferences for separate- versus same-day preoperative consultation and factors that may be associated with these preferences. Methods and Materials Patients who underwent Mohs micrographic surgery (MMS) or excision at our institution within 24months were retrospectively surveyed regarding their preferences for a separate- or same-day preoperative consultation. Procedure, tumor attributes, complications, and medications were recorded. Results Sixty-seven percent of patients preferred same-day preoperative consultation and surgery. Patients preferring same-day surgery were more likely to have a larger preoperative tumor size, whereas those preferring separate-day surgery were more likely to have had a history of complications. Limitations This was a retrospective study performed at a single academic center. Conclusion A majority of patients preferred same-day preoperative consultation and surgery. Tumor size and prior complications should be considered in preoperative planning for dermatologic surgery. C1 [Sharon, Victoria R.; Armstrong, April W.; Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA. [On, Shelbi C. Jim] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Eisen, DB (reprint author), 3301 C St,Suite 1400, Sacramento, CA 95816 USA. EM dbeisen@ucdavis.edu OI Sharon, Victoria/0000-0002-5108-8757; Eisen, Daniel/0000-0001-6741-3182 NR 10 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD FEB PY 2013 VL 39 IS 2 BP 240 EP 247 DI 10.1111/dsu.12083 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 086CV UT WOS:000314661700009 PM 23279092 ER PT J AU Damiano, ER El-Khatib, FH Zheng, H Nathan, DM Russell, SJ AF Damiano, Edward R. El-Khatib, Firas H. Zheng, Hui Nathan, David M. Russell, Steven J. TI A Comparative Effectiveness Analysis of Three Continuous Glucose Monitors SO DIABETES CARE LA English DT Article ID DIABETIC-PATIENTS; INSULIN DELIVERY; TYPE-1; PANCREAS AB OBJECTIVE-To compare three continuous glucose monitoring (CGM) devices in subjects with type 1 diabetes under closed-loop blood glucose (BG) control. RESEARCH DESIGN AND METHODS-Six subjects with type 1 diabetes (age 52 +/- 14 years, diabetes duration 32 +/- 14 years) each participated in two 51-h closed-loop BG control experiments in the hospital. Venous plasma glucose (PG) measurements (GlucoScout, International Biomedical) obtained every 15 min (2,360 values) were paired in time with corresponding CGM glucose (CGMG) measurements obtained from three CGM devices, the Navigator (Abbott Diabetes Care), the Seven Plus (DexCom), and the Guardian (Medtronic), worn simultaneously by each subject. Errors in paired PG-CGMG measurements and data reporting percentages were obtained for each CGM device. RESULTS-The Navigator had the best overall accuracy, with an aggregate mean absolute relative difference (MARD) of all paired points of 11.8 +/- 11.1% and an average MARD across all 12 experiments of 11.8 +/- 3.8%. The Seven Plus and Guardian produced aggregate MARDs of all paired points of 16.5 +/- 17.8% and 20.3 +/- 18.0%, respectively, and average MARDs across all 12 experiments of 16.5 +/- 6.7% and 20.2 +/- 6.8%, respectively. Data reporting percentages, a measure of reliability, were 76% for the Seven Plus and nearly 100% for the Navigator and Guardian. CONCLUSIONS-A comprehensive head-to-head-to-head comparison of three CGM devices for BG values from 36 to 563 mg/dL revealed marked differences in performance characteristics that include accuracy, precision, and reliability. The Navigator outperformed the other two in these areas. Diabetes Care 36:251-259, 2013 C1 [Damiano, Edward R.; El-Khatib, Firas H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Nathan, David M.; Russell, Steven J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Nathan, David M.; Russell, Steven J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nathan, David M.; Russell, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM sjrussell@partners.org FU National Institutes of Health (NIH); General Clinical Research Center and Clinical and Translational Science Center programs from the NIH National Center for Research Resources [M01-RR01066, UL1-RR025758]; Juvenile Diabetes Research Foundation [22-2009-798]; Charlton Fund for Innovative Research in Diabetes FX This study was supported by National Institutes of Health (NIH) Grant R01-DK085633 to E.R.D., grants M01-RR01066 and UL1-RR025758 through the General Clinical Research Center and Clinical and Translational Science Center programs from the NIH National Center for Research Resources, Clinical Investigations Research Grant 22-2009-798 to E.R.D. from the Juvenile Diabetes Research Foundation, and a grant to D.M.N. from the Charlton Fund for Innovative Research in Diabetes. NR 9 TC 34 Z9 34 U1 0 U2 22 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2013 VL 36 IS 2 BP 251 EP 259 DI 10.2337/dc12-0070 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083MA UT WOS:000314467100021 PM 23275350 ER PT J AU Pomeroy, J Renstrom, F Gradmark, AM Mogren, I Persson, M Bluck, L Wright, A Kahn, SE Domellof, M Franks, PW AF Pomeroy, Jeremy Renstrom, Frida Gradmark, Anna M. Mogren, Ingrid Persson, Margareta Bluck, Les Wright, Antony Kahn, Steven E. Domellof, Magnus Franks, Paul W. TI Maternal Physical Activity and Insulin Action in Pregnancy and Their Relationships With Infant Body Composition SO DIABETES CARE LA English DT Article ID SENSITIVITY; WOMEN; SECRETION AB OBJECTIVE-We sought to assess the association between maternal gestational physical activity and insulin action and body composition in early infancy. RESEARCH DESIGN AND METHODS-At 28-32 weeks' gestation, pregnant women participating in an observational study in Sweden underwent assessments of height, weight, and body composition, an oral glucose tolerance test, and 10 days of objective physical activity assessment. Thirty mothers and infants returned at 11-19 weeks postpartum. Infants underwent assessments of weight, length, and body composition. RESULTS-Early insulin response was correlated with total physical activity (r = 0.47; P = 0.007). Early insulin response (r = -0.36; P = 0.045) and total physical activity (r = 0.52; P = 0.037) were also correlated with infant fat-free mass. No maternal variable was significantly correlated with infant adiposity. CONCLUSIONS-The relationships between maternal physical activity, insulin response, and infant fat-free mass suggest that physical activity during pregnancy may affect metabolic outcomes in the mother and her offspring. Diabetes Care 36:267-269, 2013 C1 [Pomeroy, Jeremy; Renstrom, Frida; Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Pomeroy, Jeremy] NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. [Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Renstrom, Frida; Gradmark, Anna M.; Franks, Paul W.] Umea Univ, Med Sect, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Umea, Sweden. [Mogren, Ingrid; Persson, Margareta] Umea Univ, Dept Clin Sci, Obstet & Gynecol Unit, Umea, Sweden. [Persson, Margareta] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden. [Bluck, Les; Wright, Antony] MRC Human Nutr Res, Cambridge, England. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Domellof, Magnus] Umea Univ, Dept Pediat, Umea, Sweden. RP Franks, PW (reprint author), Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. EM jeremy.pomeroy@nih.gov; paul.franks@med.lu.se RI Domellof, Magnus/E-5307-2011; OI Domellof, Magnus/0000-0002-0726-7029; Mogren, Ingrid/0000-0003-2985-1135; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Torsten Soderberg foundation; Ragnar Soderberg foundation; Fredrik and Ingrid Thurings Foundation; Vasterbotten regional health authority; Medical Research Council Unit [U1059]; National Institute of Diabetes and Digestive and Kidney Diseases; U.S. Department of Veterans Affairs FX This study was a preparatory project for the LifeGene Study (www.lifegene.se) and was funded by the Torsten and Ragnar Soderberg foundations, Fredrik and Ingrid Thurings Foundation, and Vasterbotten regional health authority (all grants to P.W.F.). The stable isotope measurements were conducted under the Medical Research Council Unit Program U1059. J.P. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. S.E.K. was supported in part by the U.S. Department of Veterans Affairs. NR 9 TC 8 Z9 8 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2013 VL 36 IS 2 BP 267 EP 269 DI 10.2337/dc12-0885 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083MA UT WOS:000314467100023 PM 22966095 ER PT J AU Wander, PL Boyko, EJ Leonetti, DL McNeely, MJ Kahn, SE Fujimoto, WY AF Wander, Pandora L. Boyko, Edward J. Leonetti, Donna L. McNeely, Marguerite J. Kahn, Steven E. Fujimoto, Wilfred Y. TI Change in Visceral Adiposity Independently Predicts a Greater Risk of Developing Type 2 Diabetes Over 10 Years in Japanese Americans SO DIABETES CARE LA English DT Article ID BODY-FAT DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; LIFETIME RISK; MELLITUS; OBESITY; MEN; CLASSIFICATION; DISEASE; WEIGHT AB OBJECTIVE-Visceral adiposity is an important risk factor for cardiovascular disease and type 2 diabetes. We sought to determine whether change in intraabdominal fat area (IAF) over time predicts subsequent development of diabetes. RESEARCH DESIGN AND METHODS-We followed up 436 nondiabetic Japanese-American subjects (mean age 51.9 years, mean BMI 24.2 kg/m(2), 54% male) for development of diabetes. We fit a logistic regression model to examine the association over a 10-year follow-up between change in IAF at 5-year follow-up and other fat areas (measured by computed tomography) and development of incident diabetes, adjusted for age, sex, family history of diabetes in a first-degree relative, second-generation versus third-generation Japanese American (Nisei vs. Sansei), baseline IAF, BMI, weight change over time, smoking status, physical activity level, and subcutaneous fat (SCF) depot areas. RESULTS-Cumulative incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm(2). An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds of diabetes over 10 years (OR = 1.65, 95% CI 1.21-2.25) after adjusting for the above covariates. This association was also independent of changes in thoracic, thigh, and abdominal SCF, as well as change in weight. CONCLUSIONS-We conclude that baseline IAF and accumulation of fat in this area over time are independent predictors of the development of type 2 diabetes in Japanese Americans. Diabetes Care 36:289-293, 2013 C1 [Wander, Pandora L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Boyko, Edward J.; McNeely, Marguerite J.; Kahn, Steven E.; Fujimoto, Wilfred Y.] Univ Washington, Dept Med, Seattle, WA USA. [Boyko, Edward J.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Wander, PL (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. EM lwander@u.washington.edu OI Wander, Pandora/0000-0003-3671-1464; Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; Diabetes Research Center [DK-17047]; Clinical Nutrition Research Unit [DK-35816]; General Clinical Research Center at the University of Washington [RR-00037] FX This work was supported by National Institutes of Health grants DK-31170, HL-49293, and DK-02654 and by facilities and services provided by the Diabetes Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound Health Care System provides support for the involvement of E.J.B. and S.E.K. in this research. NR 33 TC 21 Z9 21 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2013 VL 36 IS 2 BP 289 EP 293 DI 10.2337/dc12-0198 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083MA UT WOS:000314467100028 PM 22966093 ER PT J AU Willette, AA Xu, GF Johnson, SC Birdsill, AC Jonaitis, EM Sager, MA Hermann, BP La Rue, A Asthana, S Bendlin, BB AF Willette, Auriel A. Xu, Guofan Johnson, Sterling C. Birdsill, Alex C. Jonaitis, Erin M. Sager, Mark A. Hermann, Bruce P. La Rue, Asenath Asthana, Sanjay Bendlin, Barbara B. TI Insulin Resistance, Brain Atrophy, and Cognitive Performance in Late Middle-Aged Adults SO DIABETES CARE LA English DT Article ID GRAY-MATTER VOLUME; ALZHEIMERS-DISEASE; RHESUS-MONKEYS; DYSFUNCTION; RECEPTOR; GLUCOSE; BETA; MORPHOMETRY; METABOLISM; MECHANISMS AB OBJECTIVE-Insulin resistance dysregulates glucose uptake and other functions in brain areas affected by Alzheimer disease. Insulin resistance may play a role in Alzheimer disease etiopathogenesis. This longitudinal study examined whether insulin resistance among late middle-aged, cognitively healthy individuals was associated with 1) less gray matter in Alzheimer disease-sensitive brain regions and 2) worse cognitive performance. RESEARCH DESIGN AND METHODS-Homeostasis model assessment of insulin resistance, gray matter volume, and the Rey Auditory Verbal Learning Test (RAVLT) were acquired in 372 participants at baseline and a consecutive subset of 121 individuals similar to 4 years later. Voxel-based morphometry and tensor-based morphometry were used, respectively, to test the association of insulin resistance with baseline brain volume and progressive gray matter atrophy. RESULTS-Higher insulin resistance predicted less gray matter at baseline and 4 years later in medial temporal lobe, prefrontal cortices, precuneus, and other parietal gyri. A region-of-interest analysis, independent of the voxel-wise analyses, confirmed that higher insulin resistance was related to medial temporal lobe atrophy. Atrophy itself corresponded to cognitive deficits in the RAVLT. Temporal lobe atrophy that was predicted by higher insulin resistance significantly mediated worse RAVLT encoding performance. CONCLUSIONS-These results suggest that insulin resistance in an asymptomatic, late middle-aged cohort is associated with progressive atrophy in regions affected by early Alzheimer disease. Insulin resistance may also affect the ability to encode episodic information by negatively influencing gray matter volume in medial temporal lobe. Diabetes Care 36:443-449, 2013 C1 [Willette, Auriel A.; Xu, Guofan; Johnson, Sterling C.; Birdsill, Alex C.; Asthana, Sanjay; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Willette, Auriel A.; Johnson, Sterling C.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Willette, Auriel A.; Xu, Guofan; Johnson, Sterling C.; Birdsill, Alex C.; Jonaitis, Erin M.; Sager, Mark A.; Hermann, Bruce P.; La Rue, Asenath; Asthana, Sanjay; Bendlin, Barbara B.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Xu, Guofan] Univ Wisconsin, Dept Nucl Med, Madison, WI USA. [Jonaitis, Erin M.; Sager, Mark A.; Hermann, Bruce P.; La Rue, Asenath; Asthana, Sanjay] Wisconsin Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI USA. RP Bendlin, BB (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institutes of Health [R01AG21155, R01AG027161, P50AG033514] FX This study was supported by National Institutes of Health grants R01AG21155, R01AG027161, and P50AG033514. Portions of data collection and analysis were facilitated by resources from the Veterans Administration at the William S. Middleton Memorial Veterans Hospital and Geriatric Research Education and Clinical Center in Madison, Wisconsin. NR 40 TC 48 Z9 48 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2013 VL 36 IS 2 BP 443 EP 449 DI 10.2337/dc12-0922 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083MA UT WOS:000314467100050 PM 23069842 ER PT J AU Shameli, A Yamanouchi, J Tsai, S Yang, Y Clemente-Casares, X Moore, A Serra, P Santamaria, P AF Shameli, Afshin Yamanouchi, Jun Tsai, Sue Yang, Yang Clemente-Casares, Xavier Moore, Anna Serra, Pau Santamaria, Pere TI IL-2 promotes the function of memory-like autoregulatory CD8+T cells but suppresses their development via FoxP3+Treg cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Autoregulatory T-cell memory; CD122; FoxP3+CD25+Treg cells; IL-2; Type 1 diabetes ID CD8(+) T-CELLS; NONOBESE DIABETIC MICE; SECONDARY EXPANSION; AVIDITY MATURATION; CD8-T-CELL MEMORY; CD4-T-CELL HELP; BONE-MARROW; RESPONSES; PROLIFERATION; AUTOIMMUNITY AB IL-2 plays a critical role in both effector T-cell development and FoxP3+CD4+ Treg-cell homeostasis. A reduction in Il2 transcription results in impaired FoxP3+CD4+ Treg-cell recruitment and function, and accounts for the association between murine Il2 and type 1 diabetes (T1D). The progression of T1D elicits a disease-countering negative feedback regulatory loop that involves the differentiation of low-avidity autoreactive CD8+ T cells into memory-like autoregulatory T cells in a CD4+ Th-dependent manner. Since these auto-regulatory T cells express IL-2R (CD122), we hypothesized that their development might also be regulated by IL-2. Here, we investigate the effects of differences in IL-2 expression on this autoregulatory subset. We show that decreased IL-2 production impairs the regulatory capacity of memory-like autoregulatory CD8+CD122+ T cells. Surprisingly, we also find that a reduction in IL-2 production capacity increases memory autoregulatory CD8+ T-cell formation indirectly, by decreasing the development and function of FoxP3+ Treg cells in nonobese diabetic mice. These results illustrate a complex homeostatic interplay between IL-2, CD4+ Th cells, FoxP3+CD4+ Treg cells and autoregulatory CD8+ T-cell memory whereby IL-2 controls the function of both Treg-cell subsets, but IL-2-potentiation of FoxP3+CD4+ Treg-cell function results in the suppression of CD4+ Th-cell activation and autoregulatory memory CD8+ T-cell formation. C1 [Shameli, Afshin; Yamanouchi, Jun; Tsai, Sue; Yang, Yang; Clemente-Casares, Xavier; Santamaria, Pere] Univ Calgary, JMDRC, Calgary, AB T2N 4N1, Canada. [Shameli, Afshin; Yamanouchi, Jun; Tsai, Sue; Yang, Yang; Clemente-Casares, Xavier; Santamaria, Pere] Univ Calgary, Dept Microbiol, Snyder Inst Chron Dis, Calgary, AB T2N 4N1, Canada. [Shameli, Afshin; Yamanouchi, Jun; Tsai, Sue; Yang, Yang; Clemente-Casares, Xavier; Santamaria, Pere] Univ Calgary, Dept Immunol, Snyder Inst Chron Dis, Calgary, AB T2N 4N1, Canada. [Shameli, Afshin; Yamanouchi, Jun; Tsai, Sue; Yang, Yang; Clemente-Casares, Xavier; Santamaria, Pere] Univ Calgary, Dept Infect Dis, Snyder Inst Chron Dis, Calgary, AB T2N 4N1, Canada. [Yang, Yang] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Moore, Anna] Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Dept Radiol, Charlestown, MA USA. [Serra, Pau; Santamaria, Pere] Hosp Clin Barcelona, Ctr Esther Koplowitz, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. RP Santamaria, P (reprint author), Univ Calgary, Dept Microbiol Immunol & Infect Dis, HRIC 4A22,3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM psantama@ucalgary.ca FU Canadian Institutes of Health Research; Alberta Innovates-Health Solutions (AIHS); Diabetes Association (Foothills); Canadian Diabetes Association FX We thank J. Luces and R. Barasi for technical assistance, and L. Kennedy and L. Robertson for flow cytometry. This work was supported by the Canadian Institutes of Health Research. A. S. and S. T. were supported by studentships from Alberta Innovates-Health Solutions (AIHS). P. Santamaria is a Scientist of AIHS and a Scholar of the Juvenile Diabetes Research Foundation and Instituto de Investigaciones Sanitarias Carlos III. P. Serra is an investigator of the Ramon y Cajal re-integration program of the Ministerio de Economia y Competitividad of Spain. The JMDRC was supported by the Diabetes Association (Foothills) and the Canadian Diabetes Association. NR 40 TC 12 Z9 13 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 2013 VL 43 IS 2 BP 394 EP 403 DI 10.1002/eji.201242845 PG 10 WC Immunology SC Immunology GA 091LN UT WOS:000315051100013 PM 23180662 ER PT J AU Gurol, ME AF Gurol, M. E. TI Cerebral hypoperfusion and white matter disease in healthy elderly and patients with Alzheimer's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Editorial Material ID AMYLOID ANGIOPATHY; HYPERINTENSITIES; FLOW C1 [Gurol, M. E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gurol, M. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gurol, ME (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM megurol@partners.org RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU NIA NIH HHS [R01 AG026484, R01 AG26484]; NINDS NIH HHS [T32 NS048005] NR 11 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD FEB PY 2013 VL 20 IS 2 BP 214 EP 215 DI 10.1111/j.1468-1331.2012.03865.x PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 090RO UT WOS:000314997200005 PM 22958114 ER PT J AU Kumar, KR Ramirez, A Gobel, A Kresojevic, N Svetel, M Lohmann, K Sue, CM Rolfs, A Mazzulli, JR Alcalay, RN Krainc, D Klein, C Kostic, V Grunewald, A AF Kumar, K. R. Ramirez, A. Goebel, A. Kresojevic, N. Svetel, M. Lohmann, K. Sue, C. M. Rolfs, A. Mazzulli, J. R. Alcalay, R. N. Krainc, D. Klein, C. Kostic, V. Gruenewald, A. TI Glucocerebrosidase mutations in a Serbian Parkinson's disease population SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE Gaucher disease; GBA; glucocerebrosidase; Parkinson's disease; Serbian ID GAUCHER-DISEASE; N370S; GENE; HAPLOTYPE AB Background and purpose: To screen for glucocerebrosidase (GBA) mutations in a Serbian Parkinson's disease (PD) population. Methods: Glucocerebrosidase exons 8-11 harbouring the most common mutations were sequenced in 360 patients with PD and 348 controls from Serbia. Haplotype analysis was performed for the N370S mutation and compared with German and Ashkenazi Jewish carriers. Results: Glucocerebrosidase mutations were significantly more frequent in patients with PD (21/360; 5.8%) vs. controls (5/348; 1.4%; OR = 4.25; CI, 1.58-11.40; P = 0.0041). Two patients with PD carried homozygous or compound heterozygous mutations in GBA. The N370S mutation accounted for about half of the mutated alleles in patients (10/23) but was absent amongst controls. Three novel variants were detected including two non-synonymous variants (D380V, N392S) in the patient group and one synonymous change (V459V) in a control. Carriers of the D409H mutation were also sequenced for H255Q, and all were found to carry the [D409H; H255Q] double-mutant allele. Genotyping suggested a common haplotype for all N370S carriers. Conclusion: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population. C1 [Kumar, K. R.; Ramirez, A.; Goebel, A.; Lohmann, K.; Klein, C.; Gruenewald, A.] Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, D-23538 Lubeck, Germany. [Kumar, K. R.; Sue, C. M.] Royal N Shore Hosp, Kolling Inst Med Res, Dept Neurogenet, Sydney, NSW, Australia. [Kumar, K. R.; Sue, C. M.] Univ Sydney, Sydney, NSW 2006, Australia. [Ramirez, A.] Univ Hosp Bonn, Dept Psychiat, Bonn, Germany. [Kresojevic, N.; Svetel, M.; Kostic, V.] Univ Belgrade, Sch Med, Inst Neurol CCS, Belgrade, Serbia. [Rolfs, A.] Univ Rostock, Albrecht Kossel Inst Neuroregenerat, D-18055 Rostock, Germany. [Mazzulli, J. R.; Krainc, D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Charlestown, MA USA. [Alcalay, R. N.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. RP Klein, C (reprint author), Med Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM Christine.klein@neuro.uni-luebeck.de FU Dora Lush National Health and Medical Research Council of Australia; Ministry of Education and Science of the Republic of Serbia [175090]; Australian Brain Foundation; Parkinson's NSW Foundation; Australian Department of Health and Aging; National Health and Medical Research Council of Australia [1010839]; National Institutes of Health [F32NS066730, R01NS051303]; Parkinson's Disease Foundation; Brookdale Foundation; National Parkinson Foundation; GENE-PARK [EU-LSHB-CT-. 2006-037544]; Novartis Pharma; Volkswagen Foundation; Hermann and Lilly Schilling Foundation; BMBF [01GI0201]; Boehringer Ingelheim; Centogene; Fritz Thyssen Foundation; Dystonia Medical Research Foundation FX Kishore R. Kumar receives funding from the Dora Lush National Health and Medical Research Council of Australia postgraduate scholarship. Alfredo Ramirez and Anna Gobel report no disclosures. Nikola Kresojevic and Marina Svetel are supported by a scientific grant from the Ministry of Education and Science of the Republic of Serbia (Grant #175090). Carolyn M. Sue receives support from the Australian Brain Foundation, the Parkinson's NSW Foundation, the Australian Department of Health and Aging and the National Health and Medical Research Council of Australia (Grant #1010839). Joseph R. Mazzulli has received support from the National Institutes of Health (Grant F32NS066730). Roy N. Alcalay receives support from the Parkinson's Disease Foundation H. Houston Merritt Fellowship in Movement Disorders and has also received publishing royalties for Early Onset Parkinson's Disease (Cyberounds, 2010) and research support from the Brookdale Foundation. Dimitri Krainc has received support from the National Institutes of Health (Grant R01NS051303), the National Parkinson Foundation, and a GENE-PARK (EU-LSHB-CT-. 2006-037544) grant and research support from Novartis Pharma. Christine Klein is supported by grants from the Volkswagen Foundation (Lichtenberg Grant), the Hermann and Lilly Schilling Foundation and from the BMBF (01GI0201) and has also received consulting fees from Boehringer Ingelheim and Centogene and speaker honoraria from Boehringer Ingelheim and Merz Pharma. Vladimir S. Kostic is supported by a scientific grant from the Ministry of Education and Science of the Republic of Serbia (Grant #175090) and has served on a scientific advisory board for Boehringer Ingelheim and received speaker honoraria from Novartis, Boehringer Ingelheim, Libra (Merck Serono), Lundbeck Inc. and GlaxoSmithKline. Anne Grunewald receives funding from the Fritz Thyssen Foundation and the Dystonia Medical Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 13 TC 18 Z9 18 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD FEB PY 2013 VL 20 IS 2 BP 402 EP 405 DI 10.1111/j.1468-1331.2012.03817.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 090RO UT WOS:000314997200033 PM 22812582 ER PT J AU Schon, K Ross, RS Hasselmo, ME Stern, CE AF Schon, Karin Ross, Robert S. Hasselmo, Michael E. Stern, Chantal E. TI Complementary roles of medial temporal lobes and mid-dorsolateral prefrontal cortex for working memory for novel and familiar trial-unique visual stimuli SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE familiarity monitoring; hippocampus; human; parahippocampal cortex; retrieval success ID LONG-TERM-MEMORY; LATERAL FRONTAL-CORTEX; EVENT-RELATED FMRI; PARIETAL CORTEX; EPISODIC MEMORY; RECOGNITION MEMORY; ENTORHINAL CORTEX; DELAYED MATCH; RELATIONAL INFORMATION; LOCATION ASSOCIATIONS AB It has been suggested that working memory (WM) for novel information requires the medial temporal lobes (MTL), but is not necessary for WM for familiar stimuli. In previous studies that directly compared WM for novel and familiar stimuli, only the novel stimuli were trial-unique. Here, 16 young human subjects performed a Sternberg WM task with visual scenes while in a functional magnetic resonance imaging scanner. All task stimuli were trial-unique, but were either new (Novel condition) or previously learned (Familiar condition). This design allowed investigation of whether MTL and prefrontal cortex (PFC) activity is related specifically to the novelty/familiarity of the stimuli or to their trial-unique status during WM. We observed greater hippocampal and parahippocampal activity during encoding and maintenance for novel than for familiar stimuli. In contrast, right mid-dorsolateral PFC (dlPFC) activity was greater during encoding of familiar than novel stimuli. The mid-dlPFC was not recruited during maintenance or for retrieval when the Familiar condition was contrasted with the Novel condition. However, left mid-dlPFC activity was present at retrieval when correct Match trials (i.e. hits) were contrasted with correct Non-match trials (i.e. correct rejections) for the Novel condition. The results support the hypothesis that MTL regions are required for the encoding and maintenance of novel stimuli during WM, demonstrating that the observed MTL activity is not related to the trial-uniqueness of the stimuli per se. Furthermore, the observed activation pattern in mid-dlPFC suggests a role for the mid-dlPFC in executive control-associated processes related to monitoring of scene familiarity at encoding and retrieval during WM. C1 [Schon, Karin; Ross, Robert S.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Dept Psychol, CELEST, Boston, MA 02215 USA. [Schon, Karin; Ross, Robert S.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, CELEST, Boston, MA 02215 USA. [Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Schon, K (reprint author), Boston Univ, Dept Psychol, CELEST, 64 Cummington St, Boston, MA 02215 USA. EM kschon@bu.edu OI Schon, Karin/0000-0003-2963-8449; Ross, Robert/0000-0002-3987-881X; Hasselmo, Michael/0000-0002-9925-6377 FU CELEST, an NSF Science of Learning Center [SBE 0354278]; Silvio O. Conte Center for Neuroscience Research [NIH P50 MH094263]; Boston University Undergraduate Research Opportunities Program; [P41RR14075] FX This work was supported by CELEST, an NSF Science of Learning Center (SBE 0354278), by the Silvio O. Conte Center for Neuroscience Research (NIH P50 MH094263) and by the Boston University Undergraduate Research Opportunities Program (Julie Olofson). Imaging data were collected at the Athinoula A. Martinos Center for Biomedical Imaging in Charlestown, MA, USA (supported by P41RR14075). We would like to thank Yakeel Quiroz and Julie Olofson for help with data collection and preprocessing, and Julie Olofson and Friederike Thiel for help with collecting stimuli, putting together the behavioral tasks and for initial behavioral piloting. The authors declare that they have no conflict of interest. NR 93 TC 7 Z9 7 U1 1 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2013 VL 37 IS 4 BP 668 EP 678 DI 10.1111/ejn.12062 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 091YM UT WOS:000315085700017 PM 23167976 ER PT J AU Parikh, RB Alba, GA Zukerberg, LR AF Parikh, Ravi B. Alba, George A. Zukerberg, Lawrence R. TI Tense Ascites in a Postpartum Woman SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Parikh, Ravi B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alba, George A.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Parikh, RB (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2013 VL 144 IS 2 BP 272 EP 467 DI 10.1053/j.gastro.2012.08.025 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086VL UT WOS:000314716300016 PM 23253295 ER PT J AU Wong, GS Habibollahi, P Heidari, P Lee, JS Klein-Szanto, AJ Waldron, TJ Gimotty, P Nakagawa, H Taylor, PR Wang, TC Mahmood, U Rustgi, AK AF Wong, Gabrielle S. Habibollahi, Peiman Heidari, Pedram Lee, Ju-Seog Klein-Szanto, Andres J. Waldron, Todd J. Gimotty, Phyllis Nakagawa, Hiroshi Taylor, Philip R. Wang, Timothy C. Mahmood, Umar Rustgi, Anil K. TI Optical Imaging of Periostin Enables Early Endoscopic Detection and Characterization of Esophageal Cancer in Mice SO GASTROENTEROLOGY LA English DT Article DE Mouse Model; Esophageal Cancer; Extracellular; Matrix; POSTN; Tumor Microenvironment ID TUMOR MICROENVIRONMENT; CELL; IDENTIFICATION; INVASION AB Imaging strategies that detect early stage esophageal squamous cell carcinoma (ESCC) could improve clinical outcomes, when combined with endoscopic approaches. Periostin is an integrin-binding protein that is important in the tumor microenvironment. We created a fluorescent-labeled antibody that recognizes periostin and binds specifically to ESCC xenograft tumors in mice. In L2-cre; p120ctnLoxP/LoxP mice, which develop squamous cell cancers that resemble human ESCC, we visualized the probe in preneoplastic and neoplastic esophageal lesions using near-infrared fluorescent imaging with upper-gastrointestinal endoscopy. Periostin might be a biomarker of the esophageal tumor microenvironment that can be used to detect preneoplastic lesions. C1 [Wong, Gabrielle S.; Waldron, Todd J.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Wong, Gabrielle S.; Waldron, Todd J.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Wong, Gabrielle S.; Waldron, Todd J.; Gimotty, Phyllis; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gimotty, Phyllis] Univ Penn, Ctr Clin Epidemiol & Biostat, Div Biostat, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Habibollahi, Peiman; Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Klein-Szanto, Andres J.] Fox Chase Canc Ctr, Dept Pathol & Canc Biol, Philadelphia, PA 19111 USA. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. [Wang, Timothy C.] Columbia Univ, Med Ctr, Dept Med, Div Digest & Liver Dis, New York, NY USA. [Wang, Timothy C.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Rustgi, AK (reprint author), Univ Penn, 951 BRB,421 Curie Blvd, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu FU National Institutes of Health/NCI [P01-CA098101, U01-CA14305603]; National Institutes of Health [T32-CA115299, F32-CA162719]; National Institutes of Health/NIDDK [T32-DK007066]; National Institutes of Health/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30DK050306]; American Cancer Society [RP-10-033-01-CCE]; Intramural Research Program of the US National Institutes of Health, NCI; Division of Cancer Epidemiology and Genetics FX Supported by National Institutes of Health/NCI grant P01-CA098101, National Institutes of Health grant T32-CA115299, National Institutes of Health/NIDDK (T32-DK007066), National Institutes of Health (F32-CA162719), National Institutes of Health/NCI grant U01-CA14305603, National Institutes of Health/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30DK050306), American Cancer Society (RP-10-033-01-CCE), and the Intramural Research Program of the US National Institutes of Health, NCI, and the Division of Cancer Epidemiology and Genetics. NR 15 TC 11 Z9 12 U1 1 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2013 VL 144 IS 2 BP 294 EP 297 DI 10.1053/j.gastro.2012.10.030 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086VL UT WOS:000314716300022 PM 23085486 ER PT J AU Dominitz, JA Baldwin, LM Green, P Kreuter, WI Ko, CW AF Dominitz, Jason A. Baldwin, Laura-Mae Green, Pamela Kreuter, William I. Ko, Cynthia W. TI Regional Variation in Anesthesia Assistance During Outpatient Colonoscopy Is Not Associated With Differences in Polyp Detection or Complication Rates SO GASTROENTEROLOGY LA English DT Article DE Colorectal Cancer Screening; Cost Efficacy; Quality; Pain ID DEEP SEDATION; UNITED-STATES; GI ENDOSCOPY; PROPOFOL; POPULATION; MEDICARE; ECONOMICS; SERVICES; QUALITY; SYSTEM AB BACKGROUND & AIMS: We investigated the rate and predictors of anesthesia assistance during outpatient colonoscopy and whether anesthesia assistance is associated with colonoscopy interventions and outcomes. METHODS: We performed a retrospective cohort study using a 20% sample of Medicare administrative claims submitted during the 2003 calendar year. We analyzed data from 328,177 adults, 66 years old or older, who underwent outpatient colonoscopy examinations. RESULTS: Overall, 8.7% of outpatient colonoscopies were performed with anesthesia assistance. In multivariate analysis, independent predictors of anesthesia assistance included black race, female sex, and a nonscreening indication; anesthesia assistance increased with median income and comorbidities. General and colorectal surgeons, fewer years in their practice, and nonhospital site of service were also significantly associated with anesthesia assistance. The strongest predictor of anesthesia assistance was the Medicare carrier, with odds ratios ranging from 0.22 (95% confidence interval: 0.12-0.43) for the Arkansas carrier (crude rate 0.9%) to 9.90 (95% confidence interval: 7.92-12.39) for the Empire carrier in New York area (crude rate 35.3%) compared with the Wisconsin carrier (crude rate 4.3%). There was also considerable variation among endoscopists; 75% of providers had no colonoscopies with anesthesia assistance recorded in their dataset, and 4.5% of providers had anesthesia assistance in at least three quarters of their examinations. Anesthesia assistance was not associated with the diagnosis of polyps, the performance of biopsy or polypectomy, or complications in multivariate analyses. CONCLUSIONS: There are significant variations among regions and sites of service in anesthesia assistance during outpatient colonoscopies of Medicare beneficiaries. Although this variation has considerable economic implications, it was not associated with measures of patient risk or outcomes, such as polyp detection or procedure-related complications. C1 [Dominitz, Jason A.; Green, Pamela] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Dominitz, Jason A.; Ko, Cynthia W.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Baldwin, Laura-Mae] Univ Washington, Sch Med, Dept Family Med, Seattle, WA 98195 USA. [Kreuter, William I.] Univ Washington, Dept Hlth Serv, Sch Med, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst S111 GI, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Jason.Dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU American College of Gastroenterology; NIH [CA127659]; American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award; VA Puget Sound Health Care System, Department of Veterans Affairs FX This material is based on work supported by the VA Puget Sound Health Care System, Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.; Support was received from the American College of Gastroenterology (CWK), NIH CA127659 (CWK), and American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award (JAD). NR 30 TC 14 Z9 14 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2013 VL 144 IS 2 BP 298 EP 306 DI 10.1053/j.gastro.2012.10.038 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086VL UT WOS:000314716300023 PM 23103615 ER PT J AU Shalbueva, N Mareninova, OA Gerloff, A Yuan, JZ Waldron, RT Pandol, SJ Gukovskaya, AS AF Shalbueva, Natalia Mareninova, Olga A. Gerloff, Andreas Yuan, Jingzhen Waldron, Richard T. Pandol, Stephen J. Gukovskaya, Anna S. TI Effects of Oxidative Alcohol Metabolism on the Mitochondrial Permeability Transition Pore and Necrosis in a Mouse Model of Alcoholic Pancreatitis SO GASTROENTEROLOGY LA English DT Article DE Tissue Damage; Ethanol Toxicity; Cell Death; Exocrine Pancreas ID KAPPA-B ACTIVATION; ACINAR-CELLS; CYCLOPHILIN-D; ACETALDEHYDE METABOLISM; MOLECULAR-MECHANISMS; CYCLOSPORINE-A; ETHANOL; CALCIUM; DEATH; APOPTOSIS AB BACKGROUND & AIMS: Opening of the mitochondrial permeability transition pore (MPTP) causes loss of the mitochondrial membrane potential (Delta Psi m) and, ultimately, adenosine triphosphate depletion and necrosis. Cells deficient in cyclophilin D (CypD), a component of the MPTP, are resistant to MPTP opening, loss of Delta Psi m, and necrosis. Alcohol abuse is a major risk factor for pancreatitis and is believed to sensitize the pancreas to stressors, by poorly understood mechanisms. We investigated the effects of ethanol on the pancreatic MPTP, the mechanisms of these effects, and their role in pancreatitis. METHODS: We measured Delta Psi m in mouse pancreatic acinar cells incubated with ethanol alone and in combination with physiologic and pathologic concentrations of cholecystokinin-8 (CCK). To examine the role of MPTP, we used ex vivo and in vivo models of pancreatitis, induced in wild-type and CypD(-/-) mice by a combination of ethanol and CCK. RESULTS: Ethanol reduced basal Delta Psi m and converted a transient depolarization, induced by physiologic concentrations of CCK, into a sustained decrease in Delta Psi m, resulting in reduced cellular adenosine triphosphate and increased necrosis. The effects of ethanol and CCK were mediated by MPTP because they were not observed in CypD(-/-) acinar cells. Ethanol and CCK activated MPTP through different mechanisms-ethanol by reducing the ratio of oxidized nicotinamide adenine dinucleotide to reduced nicotinamide adenine dinucleotide, as a result of oxidative metabolism, and CCK by increasing cytosolic Ca2+. CypD(-/-) mice developed a less-severe form of pancreatitis after administration of ethanol and CCK. CONCLUSIONS: Oxidative metabolism of ethanol sensitizes pancreatic mitochondria to activate MPTP, leading to mitochondrial failure; this makes the pancreas susceptible to necrotizing pancreatitis. C1 [Shalbueva, Natalia; Mareninova, Olga A.; Gerloff, Andreas; Yuan, Jingzhen; Waldron, Richard T.; Pandol, Stephen J.; Gukovskaya, Anna S.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, Los Angeles, CA 90073 USA. [Shalbueva, Natalia] Russian Acad Sci, Inst Gen & Expt Biol, Siberian Branch, Ulan Ude, Russia. RP Gukovskaya, AS (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,Bldg 258,Room 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU Southern California Research Center for ALPD and Cirrhosis (National Institutes of Health) [P50AA11999]; Department of Veterans Affairs; National Institutes of Health [R01 DK59936, R01 AA19730] FX Supported by the Southern California Research Center for ALPD and Cirrhosis (National Institutes of Health grant P50AA11999), Department of Veterans Affairs, and in part by the National Institutes of Health (R01 grants DK59936 and AA19730). NR 42 TC 13 Z9 13 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2013 VL 144 IS 2 BP 437 EP + DI 10.1053/j.gastro.2012.10.037 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086VL UT WOS:000314716300037 PM 23103769 ER PT J AU Fitzgerald, DC Fonseca-Kelly, Z Cullimore, ML Safabakhsh, P Saris, CJM Zhang, GX Rostami, AM AF Fitzgerald, Denise C. Fonseca-Kelly, Zoe Cullimore, Melissa L. Safabakhsh, Pegah Saris, Christiaan J. M. Zhang, Guang-Xian Rostami, A. M. TI Independent and inter-dependent immunoregulatory effects of IL-27, IFN-beta eta and IL-10 in the suppression of human Th17 cells and murine Experimental Autoimmune Encephalomyelitis SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Fitzgerald, Denise C.] Queens Univ Belfast, Ctr Infect & Immun, Belfast BT7 1NN, Antrim, North Ireland. [Fonseca-Kelly, Zoe] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Cullimore, Melissa L.; Safabakhsh, Pegah; Zhang, Guang-Xian; Rostami, A. M.] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. [Saris, Christiaan J. M.] Amgen Inc, Dept Inflammat Res, Thousand Oaks, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD FEB PY 2013 VL 182 SU 1 BP S7 EP S7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 092AG UT WOS:000315090600011 ER PT J AU Wongviriyawong, C Harris, RS Greenblatt, E Winkler, T Venegas, JG AF Wongviriyawong, C. Harris, R. S. Greenblatt, E. Winkler, T. Venegas, J. G. TI Peripheral resistance: a link between global airflow obstruction and regional ventilation distribution SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE distal lung; peripheral airway; structure and function; modeling; asthma ID HYPERPOLARIZED HE-3 MRI; LUNG-MECHANICS; BRONCHIAL TREE; AIRWAYS; ASTHMA; CT; PET; BRONCHOCONSTRICTION; HETEROGENEITY; METHACHOLINE AB Wongviriyawong C, Harris RS, Greenblatt E, Winkler T, Venegas JG. Peripheral resistance: a link between global airflow obstruction and regional ventilation distribution. J Appl Physiol 114: 504-514, 2013. First published November 1, 2012; doi: 10.1152/japplphysiol.00273.2012.-Airflow obstruction and heterogeneities in airway constriction and ventilation distribution are well-described prominent features of asthma. However, the mechanistic link between these global and regional features has not been well defined. We speculate that peripheral airway resistance (R-p) may provide such a link. Structural and functional parameters are estimated from PET and HRCT images of asthmatic (AS) and nonasthmatic (NA) subjects measured at baseline (BASE) and post-methacholine challenge (POST). Conductances of 35 anatomically defined proximal airways are estimated from airway geometry obtained from high-resolution computed tomography (HRCT) images. Compliances of sublobar regions subtended by 19 most distal airways are estimated from changes in regional gas volume between two lung volumes. Specific ventilations (s(V) over dot) of these sublobar regions are evaluated from (NN)-N-13-washout PET scans. For each pathway connecting the trachea to sublobar region, values of R-p required to explain the s(V) over dot distribution and global airflow obstruction are computed. Results show that R-p is highly heterogeneous within each subject, but has average values consistent with global values in the literature. The contribution of R-p to total pathway resistance (R-T) increased substantially for POST (P < 0.0001). The fraction R-p/R-T was higher in AS than NA at POST (P < 0.0001) but similar at BASE (range: 0.960-0.997, median: 0.990). For POST, R-p/R-T range was 0.979-0.999 (NA) and 0.981-0.995 (AS). This approach allows for estimations of peripheral airway resistance within anatomically defined sublobar regions in vivo human lungs and may be used to evaluate peripheral effects of therapy in a subject specific manner. C1 [Wongviriyawong, C.; Greenblatt, E.; Winkler, T.; Venegas, J. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Harris, R. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. [Greenblatt, E.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Wongviriyawong, C (reprint author), 114 Thailand Sci Pk,Paholyothin Rd,Klong 1, Klongluang 12120, Pathumthani, Thailand. EM mint.wongviriyawong@gmail.com RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Institutes of Health [R01-HL-068011] FX This work was supported by National Institutes of Health Grant R01-HL-068011. NR 40 TC 10 Z9 10 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2013 VL 114 IS 4 BP 504 EP 514 DI 10.1152/japplphysiol.00273.2012 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 092KA UT WOS:000315118300010 PM 23123354 ER PT J AU Kalwani, NM Ong, CA Lysaght, AC Haward, SJ McKinley, GH Stankovic, KM AF Kalwani, Neil M. Ong, Cheng Ai Lysaght, Andrew C. Haward, Simon J. McKinley, Gareth H. Stankovic, Konstantina M. TI Quantitative polarized light microscopy of unstained mammalian cochlear sections SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE quantitative polarized light microscopy; cochlea; birefringence; retardance; collagen; myelin ID OPTICAL COHERENCE TOMOGRAPHY; INNER-EAR; ARTICULAR-CARTILAGE; RAT COCHLEA; BASILAR-MEMBRANE; COLLAGEN NETWORK; BIREFRINGENCE; ORIENTATION; PATHOLOGY; DISEASES AB Hearing loss is the most common sensory deficit in the world, and most frequently it originates in the inner ear. Yet, the inner ear has been difficult to access for diagnosis because of its small size, delicate nature, complex three-dimensional anatomy, and encasement in the densest bone in the body. Evolving optical methods are promising to afford cellular diagnosis of pathologic changes in the inner ear. To appropriately interpret results from these emerging technologies, it is important to characterize optical properties of cochlear tissues. Here, we focus on that characterization using quantitative polarized light microscopy (qPLM) applied to unstained cochlear sections of the mouse, a common animal model of human hearing loss. We find that the most birefringent cochlear materials are collagen fibrils and myelin. Retardance of the otic capsule, the spiral ligament, and the basilar membrane are substantially higher than that of other cochlear structures. Retardance of the spiral ligament and the basilar membrane decrease from the cochlear base to the apex, compared with the more uniform retardance of other structures. The intricate structural details revealed by qPLM of unstained cochlear sections ex vivo strongly motivate future application of polarization-sensitive optical coherence tomography to human cochlea in vivo. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) [DOI: 10.1117/1.JBO.18.2.026021] C1 [Kalwani, Neil M.; Ong, Cheng Ai; Lysaght, Andrew C.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kalwani, Neil M.; Ong, Cheng Ai; Lysaght, Andrew C.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Ong, Cheng Ai] Queen Elizabeth Hosp, ENT Dept, Kota Kinabalu 88586, Sabah, Malaysia. [Lysaght, Andrew C.; Stankovic, Konstantina M.] Harvard Massachusetts Inst Technol Joint Div Hlth, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Haward, Simon J.; McKinley, Gareth H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Haward, Simon J.] Univ Porto, Fac Engn, Ctr Estudos Fenomenos Transporte, P-4200465 Oporto, Portugal. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Konstantina_Stankovich@meei.harvard.edu RI Haward, Simon/H-8700-2013 OI Haward, Simon/0000-0002-1884-4100 FU National Institute on Deafness and other Communication Disorders [K08 DC010419, T32 DC00038]; Bertarelli Foundation; Harvard Medical School Scholars in Medicine Office; Malaysian Federal Training Scholarship; NASA Microgravity Fluid Sciences [NNX09AV99G] FX We are grateful for the support of the National Institute on Deafness and other Communication Disorders Grants K08 DC010419 (K. M. S.) and T32 DC00038 (A. C. L.), the Bertarelli Foundation (K. M. S.), the Harvard Medical School Scholars in Medicine Office (N.M.K.) and the Malaysian Federal Training Scholarship (C.A.O.). S.J.H. and G. H. M. gratefully acknowledge financial support from NASA Microgravity Fluid Sciences (Code UG) Grant NNX09AV99G. We thank Drs. Deborah Perez Fernandez and Johannes Soulages for preliminary studies. NR 50 TC 3 Z9 3 U1 0 U2 16 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD FEB PY 2013 VL 18 IS 2 AR 026021 DI 10.1117/1.JBO.18.2.026021 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 092YW UT WOS:000315159900035 PM 23407909 ER PT J AU Gillman, J Davila, J Sansgiry, S Parkinson-Windross, D Miertschin, N Mitts, B Henley, C Giordano, TP AF Gillman, Jason Davila, Jessica Sansgiry, Shubhada Parkinson-Windross, Diana Miertschin, Nancy Mitts, Beau Henley, Charles Giordano, Thomas P. TI The Effect of Conspiracy Beliefs and Trust on HIV Diagnosis, Linkage, and Retention in Young MSM with HIV SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE HIV/AIDS; adolescent; race/ethnicity; linkage to care; retention in care ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL ADHERENCE; CARE PROVIDERS; HIV/AIDS; ADOLESCENTS; PREVENTION; GOVERNMENT; INFECTION; BARRIER; ADULTS AB Conspiracy beliefs about HIV may result in delayed diagnosis, medication non-adherence, and low retention in care. The impact of such beliefs is not well described for minority youth. We assessed conspiracy beliefs, trust in physicians, and trust in the health care system in 47 HIV-infected, minority, adolescent men who have sex with men (MSM). We identified correlations of these factors with two intermediate outcomes (general self-efficacy and medication attitudes) and with three clinical outcomes (CD4 cell count at diagnosis, linkage to care, and retention in care). Greater conspiracy beliefs were associated with negative medication attitudes (r = -0.37, p = .01), while trust in physicians was correlated with positive medication attitudes (r = 0.42, p = .003). Neither conspiracy beliefs nor trust was correlated with self-efficacy, nor were they correlated with any of the three clinical outcomes. Conspiracy beliefs and lack of trust did not predict delayed diagnosis or poor linkage and retention in this population of young, minority MSM. C1 [Gillman, Jason] Baylor Univ, Methodist Hosp, Dept Med, Houston, TX 77030 USA. [Davila, Jessica; Sansgiry, Shubhada; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Davila, Jessica; Sansgiry, Shubhada; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Parkinson-Windross, Diana; Miertschin, Nancy; Giordano, Thomas P.] Harris Cty Hosp Dist, Thomas St Hlth Ctr, Houston, TX USA. [Mitts, Beau] City Houston Dept Hlth & Human Serv, Houston, TX USA. [Henley, Charles] Harris Cty Publ Hlth & Environm Serv, Houston, TX USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU PHS HHS [H97HA03786] NR 22 TC 4 Z9 4 U1 2 U2 10 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2013 VL 24 IS 1 BP 36 EP 45 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 087AZ UT WOS:000314734900008 PM 23377715 ER PT J AU Allen, JD Mars, DR Tom, L Apollon, G Hilaire, D Iralien, G Cloutier, LB Sheets, MM Zamor, R AF Allen, Jennifer D. Mars, Dana R. Tom, Laura Apollon, Guy Hilaire, Dany Iralien, Gerald Cloutier, Lindsay B. Sheets, Margaret M. Zamor, Riche TI Health Beliefs, Attitudes and Service Utilization among Haitians SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Health; health beliefs; Haitian; cancer screening ID GREEN TEA CONSUMPTION; PROSTATE-CANCER; PREVENTION; MORTALITY; COMMUNITY; KNOWLEDGE; WOMEN; DISPARITIES; SUBGROUPS; CATECHINS AB Understanding the factors that influence health beliefs, attitudes, and service use among Haitians in the United States is increasingly important for this growing population. We undertook a qualitative analysis to explore the factors related to cancer screening and utilization of health services among Haitians in Boston. Key informant interviews (n = 42) and nine focus groups (n = 78) revealed that Haitians experience unique barriers to health services. These include language barriers, unfamiliarity with preventive care, confidentiality concerns, mistrust and stigma concerning Western medicine, and a preference for natural remedies. Results suggest that many Haitians could benefit from health system navigation assistance, and highlight the need for comprehensive, rather than disease-focused programs, to decrease stigma and increase programmatic reach. Faith-based organizations, social service agencies, and Haitian media were identified as promising channels for disseminating health information. Leveraging positive cultural traditions and existing communication networks could increase the impact of Haitian health initiatives. C1 [Allen, Jennifer D.; Mars, Dana R.; Tom, Laura; Iralien, Gerald; Cloutier, Lindsay B.; Sheets, Margaret M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Allen, Jennifer D.] Dana Farber Canc Inst, Cantor Ctr Nursing & Patient Care Serv, Boston, MA 02215 USA. [Apollon, Guy] Haitian Multi Serv Ctr, Dorchester, MA USA. [Hilaire, Dany] Univ Massachusetts, Boston, MA 02125 USA. [Zamor, Riche] Romaz Consulting, Boston, MA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [1U48DP001946-01]; NCI NIH HHS [3U56CA118641-05S1, 5U56CA118641-03] NR 55 TC 11 Z9 11 U1 4 U2 18 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2013 VL 24 IS 1 BP 106 EP 119 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 087AZ UT WOS:000314734900015 PM 23377722 ER PT J AU Frakt, AB Carroll, AE AF Frakt, Austin B. Carroll, Aaron E. TI Sound Policy Trumps Politics: States Should Expand Medicaid SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID AFFORDABLE CARE ACT; MORTALITY; INSURANCE; COVERAGE; EXPANSIONS AB By virtue of the Supreme Court's decision on the constitutionality of the Patient Protection and Affordable Care Act, states may reject the law's expansion of Medicaid without losing all Medicaid funding from the federal government. The Court's ruling potentially permits a range of Medicaid options for states, including some that may be very attractive from state officials' political perspectives. In the context of the presidential campaign, the uncompensated care problem, and their concerns about costs of expansion, state officials are weighing their options, and some have already pledged to opt out of expansion. We argue that despite the politics, expansion is in fact good for patients, providers, and taxpayers, and states should therefore comply. C1 [Frakt, Austin B.] VA Boston Healthcare Syst, Boston, MA USA. Indiana Univ, Bloomington, IN 47405 USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 43 TC 6 Z9 7 U1 0 U2 10 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD FEB PY 2013 VL 38 IS 1 BP 165 EP 178 DI 10.1215/03616878-1898839 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 078YF UT WOS:000314136300008 PM 23052687 ER PT J AU Davidson, M Liu, SX Barter, P Brinton, EA Cannon, CP Gotto, AM Leary, ET Shah, S Stepanavage, M Mitchel, Y Dansky, HM AF Davidson, Michael Liu, Sherry Xueyu Barter, Philip Brinton, Eliot A. Cannon, Christopher P. Gotto, Antonio M., Jr. Leary, Elizabeth T. Shah, Sukrut Stepanavage, Michael Mitchel, Yale Dansky, Hayes M. TI Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Friedewald formula; beta quantification; VLDL cholesterol; HDL cholesterol; direct method; low density lipoprotein cholesterol; cholesteryl ester transfer protein ID DENSITY-LIPOPROTEIN CHOLESTEROL; INTEGRATED APPROACH; FAT TRANSPORT; HEALTHY-INDIVIDUALS; MECHANISMS; DISORDERS; DISEASE; RISK; GUIDELINES; HDL AB Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated with a cholesteryl ester transfer protein (CETP) inhibitor. An assay comparison study was conducted using pre and posttreatment serum samples from 280 of the 811 patients treated with the CETP inhibitor anacetrapib in the DEFINE study (determining the efficacy and tolerability of CETP inhibition with anacetrapib). After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula, Roche direct method (RDM) and Genzyme direct method (GDM) deviated from that measured by the beta-quantification (BQ) reference method by -12.2 +/- 7.5, -10.2 +/- 6.6, -10.8 +/- 8.8 mg/dl, respectively.(jlr) After treatment with anacetrapib, the FR formula and detergent-based direct methods provided lower LDL-C values than those obtained by the BQ reference method. The bias by the FR formula appeared to be due to an overestimation of VLDL-C by the TG/5 component of the formula. Evaluation of the clinical significance of these findings awaits comprehensive lipid and cardiovascular outcome data from ongoing Phase III clinical studies of anacetrapib.-Davidson, M., S. X. Liu, P. Barter, E. A. Brinton, C. P. Cannon, A. M. Gotto, Jr., E. T. Leary, S. Shah, M. Stepanavage, Y. Mitchel, and H. M. Dansky. Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib. J. Lipid Res. 2013. 54: 467-472. C1 [Davidson, Michael] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Liu, Sherry Xueyu; Shah, Sukrut; Stepanavage, Michael; Mitchel, Yale; Dansky, Hayes M.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Barter, Philip] Heart Res Inst, Sydney, NSW, Australia. [Brinton, Eliot A.] Utah Fdn Biomed Res, Salt Lake City, UT USA. [Brinton, Eliot A.] Univ Utah, Salt Lake City, UT USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. [Leary, Elizabeth T.] Pacific Biomarkers, Seattle, WA USA. RP Davidson, M (reprint author), Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. EM mdavidso@medicine.bsd.uchicago.edu FU Merck & Co., Inc., Whitehouse Station, NJ FX This study was funded by Merck & Co., Inc., Whitehouse Station, NJ. NR 24 TC 21 Z9 21 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2013 VL 54 IS 2 BP 467 EP 472 DI 10.1194/jlr.M032615 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088ZH UT WOS:000314876400016 PM 23172660 ER PT J AU Kim, DS Burt, AA Crosslin, DR Robertson, PD Ranchalis, JE Boyko, EJ Nickerson, DA Furlong, CE Jarvik, GP AF Kim, Daniel S. Burt, Amber A. Crosslin, David R. Robertson, Peggy D. Ranchalis, Jane E. Boyko, Edward J. Nickerson, Deborah A. Furlong, Clement E. Jarvik, Gail P. TI Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL SO JOURNAL OF LIPID RESEARCH LA English DT Article DE exome chip; atherosclerosis; diabetes ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; LOW-DENSITY-LIPOPROTEIN; GENOME-WIDE ASSOCIATION; CAROTID-ARTERY-DISEASE; SERUM PARAOXONASE; PARKINSONS-DISEASE; MISSING HERITABILITY; ADIPOSE-TISSUE; PON1 STATUS; CARDIOVASCULAR-DISEASE AB HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular and other human diseases. As the role of genetic variants outside of the PON gene cluster on PON1 activity is unknown, we sought to identify common and rare variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects to test for their effects on adjusted-PON1 activity. Three novel genes (FTO, ITGAL, and SERPINA12) and the PON gene cluster had SNPs associated with PON1 arylesterase (AREase) activity. These loci were carried forward for rare-variant analysis using Exome chip genotypes in an overlapping subset of 1,051 subjects using sequence kernel association testing. PON1 (P = 2.24 x 10=(-4)), PON3 (P = 0.022), FTO (P = 0.019), and SERPINA12 (P = 0.039) had both common and rare variants associated with PON1 AREase. ITGAL variants were associated with PON1 activity when using weighted sequence kernel association testing (SKAT) analysis (P = 2.63 x 10(-3)). When adjusting for the initial common variants, SERPINA12 became marginally significant (P = 0.09), whereas all other findings remained significant (P < 0.05), suggesting independent rare-variant effects. We present novel findings that common and rare variants in FTO, SERPINA12, and ITGAL predict PON1 activity. These results further link PON1 to diabetes and inflammation and may inform the role of HDL in human disease.-Kim, D. S., A. A. Burt, D. R. Crosslin, P. D. Robertson, J. E. Ranchalis, E. J. Boyko, D. A. Nickerson, C. E. Furlong, and G. P. Jarvik. Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL. J. Lipid Res. 2013. 54: 552-560. C1 [Kim, Daniel S.; Burt, Amber A.; Crosslin, David R.; Ranchalis, Jane E.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kim, Daniel S.; Crosslin, David R.; Robertson, Peggy D.; Nickerson, Deborah A.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Jarvik, GP (reprint author), Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. EM pair@u.washington.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU National Institutes of Health [RO1 HL-67406]; State of Washington Life Sciences Discovery Award; Sarnoff Cardiovascular Research Fellowship for Medical Students Award; Veteran Affairs Epidemiologic Research and Information Center Award [CSP 701S] FX This work was funded by National Institutes of Health Grant RO1 HL-67406 and a State of Washington Life Sciences Discovery Award to the Northwest Institute of Genetic Medicine. D.S.K. was supported in part by a Sarnoff Cardiovascular Research Fellowship for Medical Students Award. This work utilized resources of National Heart, Lung, and Blood Institute (NHLBI) Program for Genomic Applications, SeattleSNPs, Seattle, WA (http://pga.gs.washington.edu). Past work in this cohort and specifically E.J.B.'s involvement, was supported in part by resources from the VA Puget Sound Health Care System, Seattle, WA, including the Veteran Affairs Epidemiologic Research and Information Center Award CSP 701S. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 75 TC 12 Z9 12 U1 2 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2013 VL 54 IS 2 BP 552 EP 560 DI 10.1194/jlr.P033266 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088ZH UT WOS:000314876400026 PM 23160181 ER PT J AU Habibollahi, P van den Berg, NS Kuruppu, D Loda, M Mahmood, U AF Habibollahi, Peiman van den Berg, Nynke S. Kuruppu, Darshini Loda, Massimo Mahmood, Umar TI Metformin-an Adjunct Antineoplastic Therapy-Divergently Modulates Tumor Metabolism and Proliferation, Interfering with Early Response Prediction by F-18-FDG PET Imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE metformin; AMPK; tumor metabolic imaging; proliferation imaging ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; IN-VIVO; DIABETIC-PATIENTS; CELL-GROWTH; CANCER; ENERGY; RISK; DRUG; VITRO AB Over the last several years, epidemiologic data have suggested that the antidiabetes drug metformin (MET), an adenosine monophosphate-activated protein kinase (AMPK) activator, improves progression-free survival of patients with multiple cancers; more than 30 clinical trials are under way to confirm this finding. We postulated that the role of AMPK as a central cellular energy sensor would result in opposite effects on glucose uptake and proliferation, suggesting different roles for F-18-FDG and 3'deoxy-3'-F-18-fluorothymidine (F-18-FLT) in assessing its effectiveness as an antineoplastic agent. Methods: Colon cancer cell lines HT29 (human) and MC26 (murine) were treated for 24 or 72 h with a range of MET concentrations (0-10 mM). Western blotting was used to study the activation of AMPK after MET treatment. Glucose uptake and cell proliferation were measured by cell retention studies with either F-18-FDG or F-18-FLT. EdU (ethynyl deoxyuridine, a thymidine analog) and annexin-propidium iodide flow cytometry was performed to determine cell cycle S-phase and apoptotic changes. In vivo F-18-FDG and F-18-FLT PET images were acquired before and 24 h after MET treatment of HT29 tumor-bearing mice. Results: After 24 h of MET incubation, phosphorylated AMPK levels increased severalfold in both cell lines, whereas total AMPK levels remained unchanged. In cell retention studies, F-18-FDG uptake increased but F-18-FLT retention decreased significantly in both cell lines. The numbers of HT29 and MC26 cells in the S phase decreased 36% and 33%, respectively, after MET therapy. Apoptosis increased 10.5-fold and 5.8-fold in HT29 and MC26 cells, respectively, after 72 h of incubation with MET. PET imaging revealed increased F-18-FDG uptake (mean +/- SEM standardized uptake values were 0.71 +/- 0.03 before and 1.29 +/- 0.11 after MET therapy) (P < 0.05) and decreased (FFLT)-F-18 uptake (mean +/- SEM standardized uptake values were 1.18 +/- 0.05 before and 0.89 +/- 0.01 after MET therapy) (P < 0.05) in HT29 tumor-bearing mice. Conclusion: MET, through activation of the AMPK pathway, produces a dose-dependent increase in tumor glucose uptake while decreasing cell proliferation in human and murine colon cancer cells. Thus, changes in F-18-FDG uptake after MET treatment may be misleading. F-18-FLT imaging is a promising alternative that correlates with the tumor response. C1 [Habibollahi, Peiman; van den Berg, Nynke S.; Kuruppu, Darshini; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU National Institutes of Health grants [U01CA143056, U01CA084301, P50CA127003] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This research was supported in part by National Institutes of Health grants U01CA143056, U01CA084301, and P50CA127003. No other potential conflict of interest relevant to this article was reported. NR 32 TC 12 Z9 14 U1 0 U2 12 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 IS 2 BP 252 EP 258 DI 10.2967/jnumed.112.107011 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NI UT WOS:000314691200026 PM 23376854 ER PT J AU Gao, J Dizon, DS AF Gao, Jennifer Dizon, Don S. TI Preparing for Survivorship: Quality of Life in Breast Cancer Survivors SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Quality of Life; Breast Cancer; Cancer Therapy ID DISTRESS AB Introduction. Breast cancer affects over 200,000 women each year; however, with earlier diagnosis and more effective treatment, patients are living longer, even in the presence of metastatic disease. Current estimates place patients with breast cancer as the largest population of cancer survivors in the United States. Given the successes in treatment, quality of life (QOL) of breast cancer survivors has become a more important consideration. Aim. The aim of this study is to examine QOL throughout the cancer journey. Methods. The cancer journey will be conceptualized across disease states. Main Outcome Measures. Understanding of the longitudinal journey associated with dynamic changes in physical, mental, and psychosocial spheres that occur with cancer, cancer treatment, and the sequelae of both. Conceptualization of changes is shown through the QOL as the survivor moves through the phases of cancer. Results. QOL is not a static concept, and breast cancer survivors undergo dynamic changes in QOL starting at diagnosis, as they progress through treatment and enter posttreatment. Some domains that make up QOL (i.e., sexual functioning and role functioning) can show persistent detriments related to cancer and its treatment. Conclusions. In this article, we will provide a snapshot of some research performed to better understand the QOL of breast cancer survivors using a disease states model of breast cancer. Gao J and Dizon DS. Preparing for survivorship: quality of life in breast cancer survivors. J Sex Med 2013;10(suppl 1):16-20. C1 [Gao, Jennifer] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Dizon, Don S.] Massachusetts Gen Canc Ctr, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Massachusetts Gen Canc Ctr, Gillette Ctr Womens Canc, Boston, MA 02114 USA. EM donstevendizon@gmail.com NR 17 TC 2 Z9 2 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 SU 1 SI SI BP 16 EP 20 DI 10.1111/jsm.12029 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 088XM UT WOS:000314871200004 PM 23387908 ER PT J AU Bober, SL Carter, J Falk, S AF Bober, Sharon L. Carter, Jeanne Falk, Sandy TI Addressing Female Sexual Function after Cancer by Internists and Primary Care Providers SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Female Sexual Function; Survivorship; Cancer; Primary Care ID LOW-DOSE ESTRADIOL; QUALITY-OF-LIFE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; VAGINAL ATROPHY; OVARIAN-CANCER; THERAPY; COMMUNICATION; DYSFUNCTION; PHYSICIANS AB Introduction. There are now almost 14 million cancer survivors in the United States, and for the majority of survivors, the bulk of post-cancer medical care is provided by community primary care providers (PCPs). Sexual dysfunction is one of the most common and distressing quality of life issues facing female cancer survivors yet it has become increasingly evident that women's cancer-related sexual dysfunction often goes unaddressed, including in primary care treatment setting. Aim. Building on a model that calls for an integrative approach to treatment, the aim is to concisely review barriers and challenges of managing cancer-related female sexual dysfunction for PCPs and to offer specific and effective strategies that PCPs may use to treat common sexual problems in their female cancer survivors. Methods. Literature was reviewed for relevant publications on the topic of treating cancer-related sexual dysfunction and primary care, and interviews were conducted with experts on state-of-the-art methods for treating cancer-related sexual dysfunction. Main Outcome Measure. Clinical evidence that demonstrates the effectiveness of simple strategies to manage cancer-related female sexual dysfunction. Results. Cancer-related female sexual dysfunction does not seem to be appropriately acknowledged and addressed in primary care treatment settings. There is evidence to show that simple and effective strategies exist to ameliorate many of these problems. Conclusions. PCPs provide the bulk of survivorship care and are therefore in a critical position to initiate assessment and treatment for female survivors with cancer-related sexual dysfunction. Although PCPs are in need of increased support and preparation to manage this aspect of survivorship care, simple and effective strategies are available for PCPs to offer women as part of their clinical practice. Bober SL, Carter J, and Falk S. Addressing female sexual function after cancer by internists and primary care providers. J Sex Med 2013;10(suppl 1):112-119. C1 [Bober, Sharon L.; Falk, Sandy] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bober, Sharon L.; Falk, Sandy] Harvard Univ, Sch Med, Boston, MA USA. [Carter, Jeanne] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Bober, SL (reprint author), Dana Farber Canc Inst Psychooncol, 44 Binney St Dana 321, Boston, MA 02115 USA. EM sharon_bober@dfci.harvard.edu NR 61 TC 10 Z9 10 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 SU 1 SI SI BP 112 EP 119 DI 10.1111/jsm.12027 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 088XM UT WOS:000314871200013 PM 23387916 ER PT J AU Eberhardt, SC Carter, S Casalino, DD Merrick, G Frank, SJ Gottschalk, AR Leyendecker, JR Nguyen, PL Oto, A Porter, C Remer, EM Rosenthal, SA AF Eberhardt, Steven C. Carter, Scott Casalino, David D. Merrick, Gregory Frank, Steven J. Gottschalk, Alexander R. Leyendecker, John R. Nguyen, Paul L. Oto, Aytekin Porter, Christopher Remer, Erick M. Rosenthal, Seth A. TI ACR Appropriateness Criteria Prostate Cancer-Pretreatment Detection, Staging, and Surveillance SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; prostate cancer; imaging; detection; staging ID DIGITAL RECTAL EXAMINATION; RADICAL RETROPUBIC PROSTATECTOMY; POSITRON-EMISSION-TOMOGRAPHY; SEMINAL-VESICLE INVASION; CONTRAST-ENHANCED MRI; ENDORECTAL MR; ACTIVE SURVEILLANCE; GLEASON SCORE; TRANSRECTAL ULTRASONOGRAPHY; EXTRACAPSULAR EXTENSION AB Prostate cancer is the most common noncutaneous male malignancy in the United States. The use of serum prostate-specific antigen as a screening tool is complicated by a significant fraction of nonlethal cancers diagnosed by biopsy. Ultrasound is used predominately as a biopsy guidance tool. Combined rectal examination, prostate-specific antigen testing, and histology from ultrasound-guided biopsy provide risk stratification for locally advanced and metastatic disease. Imaging in low-risk patients is unlikely to guide management for patients electing up-front treatment. MRI, CT, and bone scans are appropriate in intermediate-risk to high-risk patients to better assess the extent of disease, guide therapy decisions, and predict outcomes. MRI (particularly with an endorectal coil and multiparametric functional imaging) provides the best imaging for cancer detection and staging. There may be a role for prostate MRI in the context of active surveillance for low-risk patients and in cancer detection for undiagnosed clinically suspected cancer after negative biopsy results. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Eberhardt, Steven C.; Carter, Scott] Univ New Mexico, Albuquerque, NM 87131 USA. [Casalino, David D.] Northwestern Univ, Chicago, IL 60611 USA. [Merrick, Gregory] Schiffler Canc Ctr, Wheeling, WV USA. [Merrick, Gregory] Wheeling Jesuit Univ, Wheeling, WV USA. [Frank, Steven J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gottschalk, Alexander R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Leyendecker, John R.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Oto, Aytekin] Univ Chicago, Chicago, IL 60637 USA. [Porter, Christopher] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Porter, Christopher] Amer Urol Assoc, Linthicum, MD USA. [Remer, Erick M.] Cleveland Clin, Cleveland, OH 44106 USA. [Rosenthal, Seth A.] Radiol Associates Sacramento, Sacramento, CA USA. RP Eberhardt, SC (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM seberhardt@salud.unm.edu NR 115 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2013 VL 10 IS 2 BP 83 EP 92 DI 10.1016/j.jacr.2012.10.021 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 090VM UT WOS:000315008100009 PM 23374687 ER PT J AU Gunn, AJ Sahani, DV Bennett, SE Choy, G AF Gunn, Andrew J. Sahani, Dushyant V. Bennett, Susan E. Choy, Garry TI Recent Measures to Improve Radiology Reporting: Perspectives From Primary Care Physicians SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiology reporting; primary care physicians; quality improvement ID REFERRING PHYSICIANS; CONSULTANT; STYLE; THINK AB Purpose: There is considerable interest in improving radiology reporting practices. It has been suggested recently that reporting practices could be improved by more direct involvement of radiologists in delivering results to patients and by making clear recommendations within the radiology report. The opinions of primary care physicians about these initiatives are not well known. The authors surveyed primary care physicians to better understand their views. Methods: An online survey was distributed to 229 primary care physicians through an internal list sewer, and responses were collected confidentially. Results: There were 100 responses (a 43.6% response rate). The majority of respondents were satisfied with radiology reporting and recommendations in general. Ninety-five percent of respondents felt that ordering physicians should deliver the results of examinations. No respondents felt that radiologists should deliver results directly to patients. Ninety-four percent of respondents felt medicolegally obligated by recommendations made by radiologists within their reports. Twenty-three percent of respondents felt more medicolegally obligated if the recommendation is set apart from the clinical impression, while 58% of respondents felt less medicolegally obligated if qualifying language is added to the recommendation. Conclusions: Primary care physicians prefer to deliver the results of examinations themselves and feel medicolegally obligated by recommendations within radiology reports, even though this seems to be influenced by the wording and location of the recommendations within reports. Radiologists should consider these factors when contemplating changes in reporting practices. C1 [Gunn, Andrew J.; Sahani, Dushyant V.; Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gunn, Andrew J.; Sahani, Dushyant V.; Bennett, Susan E.; Choy, Garry] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. [Bennett, Susan E.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol & Teleradiol, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, FND 216,55 Fruit St, Boston, MA 02114 USA. EM agunn@partners.org NR 26 TC 19 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2013 VL 10 IS 2 BP 122 EP 127 DI 10.1016/j.jacr.2012.08.013 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 090VM UT WOS:000315008100015 PM 23228373 ER PT J AU Thrall, JH AF Thrall, James H. TI Residents' and Fellows' Column: The Invisible Radiologist: An Address to a Residency Graduating Class SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,Room 216, Boston, MA 02114 USA. EM jthrall@partners.org NR 0 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2013 VL 10 IS 2 BP 153 EP 155 DI 10.1016/j.jacr.2012.07.020 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 090VM UT WOS:000315008100022 PM 23374696 ER PT J AU Benson, AB Bekaii-Saab, T Chan, E Chen, YJ Choti, MA Cooper, HS Engstrom, PF Enzinger, PC Fakih, MG Fenton, MJ Fuchs, CS Grem, JL Hunt, S Kamel, A Leong, LA Lin, E May, KS Mulcahy, MF Murphy, K Rohren, E Ryan, DP Saltz, L Sharma, S Shibata, D Skibber, JM Small, W Sofocleous, CT Venook, AP Willett, CG Gregory, KM Freedman-Cass, DA AF Benson, Al B., III Bekaii-Saab, Tanios Chan, Emily Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Engstrom, Paul F. Enzinger, Peter C. Fakih, Marwan G. Fenton, Moon J. Fuchs, Charles S. Grem, Jean L. Hunt, Steven Kamel, Ahmed Leong, Lucille A. Lin, Edward May, Kilian Salerno Mulcahy, Mary F. Murphy, Kate Rohren, Eric Ryan, David P. Saltz, Leonard Sharma, Sunil Shibata, David Skibber, John M. Small, William, Jr. Sofocleous, Constantinos T. Venook, Alan P. Willett, Christopher G. Gregory, Kristina M. Freedman-Cass, Deborah A. TI Metastatic Colon Cancer, Version 3.2013 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ADVANCED COLORECTAL-CANCER; HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; HIGH-DOSE LEUCOVORIN; PHASE-III TRIAL; FLUOROURACIL PLUS LEUCOVORIN; RANDOMIZED-TRIAL; PERITONEAL CARCINOMATOSIS; CYTOREDUCTIVE SURGERY; 1ST-LINE TREATMENT; SYSTEMIC CHEMOTHERAPY AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy. (JNCCN 2013;11:141-152) C1 [Benson, Al B., III; Mulcahy, Mary F.; Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bekaii-Saab, Tanios] Solove Res Inst, Columbus, OH USA. [Chan, Emily] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Cooper, Harry S.; Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Fakih, Marwan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Fenton, Moon J.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Grem, Jean L.] UNMC Eppley Canc Ctr, Nebraska Med Ctr, Omaha, NE USA. [Hunt, Steven] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Hunt, Steven] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kamel, Ahmed] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Lin, Edward] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Alliance, OH USA. [May, Kilian Salerno] Roswell Pk Canc Inst, Buffalo, NY USA. [Rohren, Eric; Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Saltz, Leonard; Sofocleous, Constantinos T.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Shibata, David] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Venook, Alan P.] UCSF Helen Diller Family, Ctr Comprehens Canc, San Francisco, CA USA. [Willett, Christopher G.] Duke Canc Inst, Durham, NC USA. [Gregory, Kristina M.; Freedman-Cass, Deborah A.] Natl Comprehens Canc Network, Toronto, ON, Canada. RP Benson, AB (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RI Bekaii-Saab, Tanios/E-2733-2011 NR 71 TC 57 Z9 58 U1 1 U2 14 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD FEB PY 2013 VL 11 IS 2 BP 141 EP 152 PG 12 WC Oncology SC Oncology GA 087WN UT WOS:000314795200005 PM 23411381 ER PT J AU Kornstein, SG Toups, M Rush, AJ Wisniewski, SR Thase, ME Luther, J Warden, D Fava, M Trivedi, MH AF Kornstein, Susan G. Toups, Marisa Rush, A. John Wisniewski, Stephen R. Thase, Michael E. Luther, James Warden, Diane Fava, Maurizio Trivedi, Madhukar H. TI Do Menopausal Status and Use of Hormone Therapy Affect Antidepressant Treatment Response? Findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID INTERACTIVE VOICE RESPONSE; MEASUREMENT-BASED CARE; REPORT QIDS-SR; GENDER-DIFFERENCES; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; SYMPTOMATOLOGY IDS; CLINICAL-PRACTICE; QUICK INVENTORY; SEX-DIFFERENCES AB Background: Menopausal status and use of hormonal contraception or menopausal hormone therapy (HT) may affect treatment response to selective serotonin reuptake inhibitors (SSRIs). This report evaluates whether menopausal status and use of hormonal contraceptives or menopausal HT affect outcome in women treated with citalopram. Methods: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 896 premenopausal and 544 postmenopausal women were treated with citalopram for 12-14 weeks. Baseline demographic and clinical characteristics were used in adjusted analysis of the effect of menopausal status and use of hormonal contraceptives or menopausal HT on outcomes. Remission was defined as final Hamilton Rating Scale for Depression-17 (HRSD17) <= 7 or Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16)score <= 5 and response as >= 50% decrease from the baseline QIDS-SR16 score. Results: Premenopausal and postmenopausal women differed in multiple clinical and demographic baseline variables but did not differ in response or remission rates. Premenopausal women taking hormonal contraceptives had significantly greater unadjusted remission rates on the HRSD17 and the QIDS-SR16 than women not taking contraception. Response and remission rates were not different between postmenopausal women taking vs. not taking HT. Adjusted results showed no significant difference in any outcome measure across menopause status in women who were not taking contraception/HT. There were no significant differences in adjusted results across HT status in premenopausal or postmenopausal women. Conclusions: In this study, citalopram treatment outcome was not affected by menopausal status. Hormonal contraceptives and HT also did not affect probability of good outcome. C1 [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Inst Womens Hlth, Richmond, VA 23298 USA. [Toups, Marisa; Rush, A. John; Warden, Diane; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. [Wisniewski, Stephen R.; Luther, James] Univ Pittsburgh, GSPH, Epidemiol Data Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Kornstein, SG (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Psychiat, POB 980710, Richmond, VA 23298 USA. EM skornste@vcu.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health [N01MH90003]; Bristol-Myers Squibb; Lilly; Euthymics; Forest Laboratories; Wyeth; Novartis; Boehringer-Ingelheim; Pfizer; Otsuka; Rexahn; Guilford Press; Advanced Neuromodulation Systems; AstraZeneca; Best Practice Project Management; Brain Resource Inc.; Bristol-Myers Squibb/Otsuka; Cyberonics; Forest Pharmaceuticals; Gerson Lehrman Group; GlaxoSmithKline; Jazz Pharmaceuticals; Magellan Health Services; Merck Company; Neuronetics; Novartis Pharmaceuticals; Ono Pharmaceuticals; Organon; Otsuka Pharmaceuticals; Pamlab; University of Michigan; Transcept Pharmaceuticals; Urban Institute; Wyeth Ayerst; Cyberonics Inc.; Guilford Publications; Healthcare Technology Systems; University of Texas Southwestern Medical Center; Stanley Medical Research Institute FX This project was funded by the National Institute of Mental Health under Contract No. N01MH90003 to UT Southwestern Medical Center at Dallas (Pls: A. J. R. and M. H. T.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. We appreciate the support of Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth for providing medications at no cost for this trial.; M. T. and J. L. have no conflicts of interest to report. S. G. K. has received grants/research support from the National Institute of Mental Health; Bristol-Myers Squibb; Lilly; Euthymics; Forest Laboratories; Wyeth; Novartis; Boehringer-Ingelheim; Pfizer; Otsuka; Rexahn. She has been on the advisory board or received honoraria from Pfizer; Lilly; Bristol-Myers Squibb; Forest Laboratories; Dey Pharma; Rexahn; PGxHealth; Wyeth; Takeda; Trovis; Lundbeck. She has also received book royalties from Guilford Press.; A. J. R. has received consultant fees from Advanced Neuromodulation Systems; AstraZeneca; Best Practice Project Management; Brain Resource Inc.; Bristol-Myers Squibb/Otsuka; Cyberonics; Forest Pharmaceuticals; Gerson Lehrman Group; GlaxoSmithKline; Jazz Pharmaceuticals; Magellan Health Services; Merck & Company; Neuronetics; Novartis Pharmaceuticals; Ono Pharmaceuticals; Organon; Otsuka Pharmaceuticals; Pamlab; Pfizer; The University of Michigan; Transcept Pharmaceuticals; Urban Institute; and Wyeth Ayerst; speaking fees from Cyberonics Inc.; Forest Laboratories; GlaxoSmithKline; and Otsuka; royalties from Guilford Publications; Healthcare Technology Systems; and The University of Texas Southwestern Medical Center; and research support from National Institute of Mental Health and the Stanley Medical Research Institute. He has owned shares of stock in Pfizer.; M. E. T. has provided scientific consultation to AstraZeneca; Bristol-Myers Squibb; Dey Pharma, L. P.; Eli Lilly & Company; Forest Pharmaceuticals, Inc.; Gerson Lehman Group; GlaxoSmithKline; Guidepoint Global; H. Lundbeck A/S; MedAvante, Inc.; Merck and Company; Neuronetics, Inc.; Novartis; Otsuka; Ortho-McNeil Pharmaceuticals; PamLab; Pfizer (formerly Wyeth-Ayerst Laboratories); ScheringPlough (formerly Organon, Inc.); Shire US Inc.; Supernus Pharmaceuticals; Takeda (Lundbeck); and Transcept Pharmaceuticals. He has been a member of the speakers' bureaus for AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Company; Merck and Company; and Pfizer (formerly Wyeth-Ayerst Laboratories). He receives grant funding from Eli Lilly & Company; GlaxoSmithKline; National Institute of Mental Health; and Agency for Healthcare Research and Quality, Sepracor, Inc. He has equity holdings in MedAvante, Inc., and receives royalty income from American Psychiatric Foundation, Inc.; Guilford Publications; Herald House; Oxford University Press; and W. W. Norton & Company. His wife is employed as the Group Scientific Director for Embryon, formerly Advogent, which does business with BMS and Pfizer/Wyeth. D. W. has owned stock in Pfizer, Inc. and Bristol-Myers Squibb within the last 5 years. She has also received funding from National Alliance for Research on Schizophrenia & Depression (NARSAD).; M. F. has received research support from Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite LLC; Photothera; Roche; RCT Logic, LLC; SanofiAventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories. He has provided advisory/ consulting services to Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co., Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Company; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite ~ LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc. He has speaking/publishing relationships with Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/ Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource, Corp.; Wyeth-Ayerst Laboratories. He has equity holdings (excluding mutual funds/blinded trusts) with Compellis.; He has received royalty/patent or other income for Sequential Parallel Comparison Design (SPCD) and patent application for a combination of azapirones and bupropion in Major Depressive Disorder; has received copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; and has received a patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams & Wilkins; World Scientific Publishing Co. Pte. Ltd.; M. H. T. has been a consultant for Abbott Laboratories, Inc.; Akzo (Organon Pharmaceuticals Inc.); AstraZeneca; Bayer; Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Eli Lilly & Company; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Neuronetics; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Pharmacia & Upjohn; Sepracor; Solvay Pharmaceuticals, Inc.; VantagePoint; and Wyeth-Ayerst Laboratories. He has served on speakers bureaus for Abdi Brahim; Akzo (Organon Pharmaceuticals Inc.); Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Eli Lilly & Company; Pharmacia & Upjohn; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories. He has also received grant support from BristolMyers Squibb; Cephalon, Inc.; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Eli Lilly & Company; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica; Merck; National Institute of Mental Health; NARSAD; Novartis; Pfizer Inc.; Pharmacia & Upjohn; Predix Pharmaceuticals; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories. NR 39 TC 10 Z9 11 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD FEB PY 2013 VL 22 IS 2 BP 121 EP 131 DI 10.1089/jwh.2012.3479 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 088XJ UT WOS:000314870900003 PM 23398127 ER PT J AU Cipriani, NA Kurzawa, P Mullen, J Deshpande, V Ahmad, R Nielsen, GP AF Cipriani, N. A. Kurzawa, P. Mullen, J. Deshpande, V. Ahmad, R. Nielsen, G. P. TI Prognostic Value of Subclassification of Pleomorphic Soft Tissue Sarcoma (STS): Myogenic Versus Non-Myogenic Differentiation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Greater Poland Canc Ctr, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 31 BP 10A EP 11A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300032 ER PT J AU Cipriani, NA McLaughlin, PJ Borger, DR Nielsen, GP AF Cipriani, N. A. McLaughlin, P. J. Borger, D. R. Nielsen, G. P. TI BRAF Mutation in "Sarcomas": A Possible Method To Detect Melanomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Cipriani, N. A.; McLaughlin, P. J.; Borger, D. R.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 30 BP 10A EP 10A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300031 ER PT J AU Kerr, DA Deshpande, V Kurzawa, P Nielsen, GP AF Kerr, D. A. Deshpande, V. Kurzawa, P. Nielsen, G. P. TI Chondroid Chordoma: A Chordoma Subtype with Worse Prognosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Greater Poland Canc Ctr, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 47 BP 14A EP 14A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300048 ER PT J AU Lee, YD Nardi, V Le, LP Deshpande, V Hornicek, FJ Lafrate, AJ Nielsen, GP AF Lee, Y. D. Nardi, V. Le, L. P. Deshpande, V. Hornicek, F. J. Lafrate, A. J. Nielsen, G. P. TI Array Comparative Genomic Hybridization Analysis of a Conventional Chordoma and an Adjacent Benign Notochordal Tumor Shows No Direct Lineage Relationship SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Lee, Y. D.; Nardi, V.; Le, L. P.; Deshpande, V.; Hornicek, F. J.; Lafrate, A. J.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 56 BP 16A EP 17A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300057 ER PT J AU Shah, K Zhang, Y Nielsen, GP Rosenberg, AE AF Shah, K. Zhang, Y. Nielsen, G. P. Rosenberg, A. E. TI Primary Myoepithelioma of the Orbit SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 71 BP 20A EP 20A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300072 ER PT J AU Zhang, Y Nielsen, GP Raskin, K Cipriani, N Rosenberg, AE AF Zhang, Y. Nielsen, G. P. Raskin, K. Cipriani, N. Rosenberg, A. E. TI Primary Malignant Myoepithelial Tumor of Bone SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 94 BP 25A EP 25A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300095 ER PT J AU Brachtel, EF Kerr, SE Anderson, J Zhang, Y Singh, V Erlander, MG Carey, B Highsmith, WE Schnabel, CA Dry, SM Sullivan, PS AF Brachtel, E. F. Kerr, S. E. Anderson, J. Zhang, Y. Singh, V. Erlander, M. G. Carey, B. Highsmith, W. E. Schnabel, C. A. Dry, S. M. Sullivan, P. S. TI Diagnostic Utility of a 92-Gene Classifier in Triple-Negative Breast Carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Rochester, MN USA. BioTheranostics Inc, San Diego, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 121 BP 31A EP 31A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300123 ER PT J AU Marques, RC Lerwill, MF AF Canas Marques, R. Lerwill, M. F. TI Incidence of Carcinoma and Atypia in Breast Reduction Mammoplasty Specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 EPE, Inst Portugues Oncol Lisboa Francisco Gentil, Lisbon, Portugal. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 126 BP 32A EP 32A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300128 ER PT J AU Auger, M Nayar, R Khalbuss, WE Barkan, GA Benedict, C Tambouret, R Schwartz, MR Howell, L Souers, R Hartley, A Thomas, N Moriarty, AT AF Auger, M. Nayar, R. Khalbuss, W. E. Barkan, G. A. Benedict, C. Tambouret, R. Schwartz, M. R. Howell, L. Souers, R. Hartley, A. Thomas, N. Moriarty, A. T. TI Implementation of the Bethesda System for Reporting Thyroid Cytopathology: Observations from the 2011 Thyroid Supplemental Questionnaire of the College of American Pathologists SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 McGill Univ, Montreal, PQ, Canada. McGill Unvers Hlth Ctr, Montreal, PQ, Canada. Northwestern Univ, Chicago, IL 60611 USA. NW Mem Hosp, Chicago, IL 60611 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Loyola Univ, Maywood, IL 60153 USA. Loyola Univ, Med Ctr Bedside Test, Maywood, IL 60153 USA. DCL Pathol LLC, Indianapolis, IN USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Phys Org, Houston, TX 77030 USA. Calif State Univ Sacramento, Sacramento, CA 95819 USA. Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. Coll Amer Pathologists, Northfield, MN USA. AmeriPath Indiana, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 338 BP 83A EP 83A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300341 ER PT J AU Balassanian, R Ono, JC Wool, GD Olejnik-Nave, J Mah, MM Sweeney, BJ Ljung, BM Pitman, MB AF Balassanian, R. Ono, J. C. Wool, G. D. Olejnik-Nave, J. Mah, M. M. Sweeney, B. J. Ljung, B-M Pitman, M. B. TI A Superior Technique for Cell Block Preparation for Fine Needle Aspiration SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Lab Med Consultants, Las Vegas, NV USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 340 BP 83A EP 83A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300343 ER PT J AU Linskey, K Kay, J Duncan, LM Nazarian, RM AF Linskey, K. Kay, J. Duncan, L. M. Nazarian, R. M. TI Wnt and Hedgehog Signaling Pathway Activation in Cutaneous Fibrosing Disorders: A Tissue Microarray Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UMass Mem Med Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 479 BP 116A EP 117A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300481 ER PT J AU Mochel, M Arakaki, R Wang, G Kroshinsky, D Hoang, M AF Mochel, M. Arakaki, R. Wang, G. Kroshinsky, D. Hoang, M. TI A Retrospective Histologic and Histochemical Evaluation of Cutaneous Calciphylaxis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Mochel, M.; Arakaki, R.; Wang, G.; Kroshinsky, D.; Hoang, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 482 BP 117A EP 117A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300484 ER PT J AU Prieto-Granada, CN Lezcano, C Piris, A Scoyler, R Mihm, M AF Prieto-Granada, C. N. Lezcano, C. Piris, A. Scoyler, R. Mihm, M. TI Lethal Childhood Melanoma: A Clinicopathological Study of 12 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Baystate Med Ctr, Springfield, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sydney Med Sch, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 489 BP 119A EP 119A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300491 ER PT J AU Cipriani, NA Faquin, WC Sadow, PM AF Cipriani, N. A. Faquin, W. C. Sadow, P. M. TI Clear Cell Variant of Thyroid Carcinoma: A Clinicopathologic Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Cipriani, N. A.; Faquin, W. C.; Sadow, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 542 BP 131A EP 131A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300544 ER PT J AU Agoston, AT Zheng, Y Bueno, R Lauwers, GY Odze, RD Srivastava, A AF Agoston, A. T. Zheng, Y. Bueno, R. Lauwers, G. Y. Odze, R. D. Srivastava, A. TI Clinicopathologic Predictors of Long Term and Disease-Free Survival in Esophageal Adenocarcinomas with Complete Pathologic Response to Neoadjuvant Chemoradiation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 592 BP 142A EP 142A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300594 ER PT J AU Arnason, T Pino, MS Chung, DC Sapp, HL Rayson, D Deshpande, V Zukerberg, LR AF Arnason, T. Pino, M. S. Chung, D. C. Sapp, H. L. Rayson, D. Deshpande, V. Zukerberg, L. R. TI Loss of Cables Expression in Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Pancreas, and Lung SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Queen Elizabeth II HSC, Halifax, NS, Canada. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 600 BP 143A EP 144A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300602 ER PT J AU Arnason, T Brown, I O'Brien, B Wilson, C Winter, H Lauwers, GY AF Arnason, T. Brown, I. O'Brien, B. Wilson, C. Winter, H. Lauwers, G. Y. TI Collagenous Gastritis: A Morphologic and Immunohistochemical Study of 27 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 601 BP 144A EP 144A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300603 ER PT J AU Bandla, S Peters, JH Ruff, D Chen, SM Li, CY Song, K Thoms, K Litle, VR Watson, T Chapurin, N Pennathur, A Luketich, JD Peterson, D Dulak, A Lin, L Bass, A Beer, DG Godfrey, TE Zhou, Z AF Bandla, S. Peters, J. H. Ruff, D. Chen, S-M Li, C-Y Song, K. Thoms, K. Litle, V. R. Watson, T. Chapurin, N. Pennathur, A. Luketich, J. D. Peterson, D. Dulak, A. Lin, L. Bass, A. Beer, D. G. Godfrey, T. E. Zhou, Z. TI Analysis of Columnar Lined Esophagus Reveals Less Frequent Mutations In Non-Goblet Cell Metaplasia Than intestinal Metaplasia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 URMC, Rochester, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Life Technol, Foster City, CA USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 604 BP 145A EP 145A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300606 ER PT J AU Bledsoe, JR Kamionek, M Shvetz, DE Mino-Kenudson, M AF Bledsoe, J. R. Kamionek, M. Shvetz, D. E. Mino-Kenudson, M. TI Loss of Expression of ARID1A and BRG1 in Colorectal Cancer Occurs Infrequently and Is Associated with BRAF Mutation and Microsatellite Instability SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Bledsoe, J. R.; Kamionek, M.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 608 BP 145A EP 146A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300610 ER PT J AU Bledsoe, JR Shvetz, DE Mino-Kenudson, M AF Bledsoe, J. R. Shvetz, D. E. Mino-Kenudson, M. TI Phosphorylation of EGFR in Colorectal Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Bledsoe, J. R.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 607 BP 145A EP 145A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300609 ER PT J AU Deshpande, A Deshpande, V O'Brien, MJ AF Deshpande, A. Deshpande, V. O'Brien, M. J. TI Interstitial Cells of Cajal in Gastrointestinal Leiomyoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 621 BP 149A EP 149A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300623 ER PT J AU Huang, Q Shi, J Sun, Q Yu, H Chen, J Wu, H Gold, JK Mashimo, H Yu, C Lauwers, GY AF Huang, Q. Shi, J. Sun, Q. Yu, H. Chen, J. Wu, H. Gold, J. K. Mashimo, H. Yu, C. Lauwers, G. Y. TI Small (<= 2 cm) Carcinomas in the Proximal Stomach Demonstrate Distinct Clinicopathologic Features from Those in the Distal and Corpus: A Proposal for Classification of Gastric Cancer by Location SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Nanjing Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China. VA Boston Healthcare Syst, W Roxbury, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 648 BP 155A EP 155A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300650 ER PT J AU Imamura, Y Fuchs, C Ogino, S AF Imamura, Y. Fuchs, C. Ogino, S. TI KRAS c.35G > T (p.G12V) and c.34G > C (p.G12R) Mutations Predict Shorter Survival in 1925 Colorectal Cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 651 BP 156A EP 157A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300653 ER PT J AU Kuchiba, A Lochhead, P Ogino, S AF Kuchiba, A. Lochhead, P. Ogino, S. TI Colon Cancer Nodal Staging Score: A Tool To Assess Adequacy of Nodal Harvesting in Pathology Practice SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 672 BP 161A EP 162A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300674 ER PT J AU Liang, WY Hsu, CY Arnason, T Hawkins, AT Sylla, P Lauwers, GY AF Liang, W. Y. Hsu, C. Y. Arnason, T. Hawkins, A. T. Sylla, P. Lauwers, G. Y. TI Retrospective Evaluation of Elastic Stain in the Assessment of Serosal Invasion of pT3N0Mx Colorectal Cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Vet Gen Hosp Taipei, Taipei, Taiwan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 683 BP 164A EP 165A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301008 ER PT J AU Liang, WY Arnason, T Alfaro, E Kelly, P Genevay, M Odze, RD Lauwers, GY AF Liang, W. Y. Arnason, T. Alfaro, E. Kelly, P. Genevay, M. Odze, R. D. Lauwers, G. Y. TI Morphology and Natural History of Familial Adenomatous Polyposis (FAP)-Associated Dysplastic Fundic Gland Polyps (FGPs) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 684 BP 165A EP 165A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301009 ER PT J AU Liao, X Imamura, Y Ogino, S AF Liao, X. Imamura, Y. Ogino, S. TI KRAS Codon 12, 13, 61 and 146 Mutations in 1267 Colorectal Cancers: Clinicopathological, Molecular, and Survival Analyses SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 685 BP 165A EP 165A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301010 ER PT J AU Lochhead, P Fuchs, C Ogino, S AF Lochhead, P. Fuchs, C. Ogino, S. TI Microsatellite Instability (MSI) and BRAF Mutation Tests Jointly Provide Useful Prognostic Information in 1861 Colorectal Cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 688 BP 166A EP 166A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301013 ER PT J AU Masia, R Peyton, S Lauwers, GY Brown, I AF Masia, R. Peyton, S. Lauwers, G. Y. Brown, I. TI Gastrointestinal Biopsy Findings of Autoimmune Enteropathy - A Review of 20 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Pathol Queensland, Herston, Qld, Australia. RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 690 BP 167A EP 167A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301015 ER PT J AU Nishihara, R Fuchs, C Ogino, S AF Nishihara, R. Fuchs, C. Ogino, S. TI Hereditary Predisposition to LINE-1 Hypomethylated Colorectal Cancer: Potential Clinical Utility of Tumor LINE-1 Methylation Test for Familial Cancer Risk Assessment SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 698 BP 169A EP 169A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301023 ER PT J AU Ogino, S Imamura, Y Fuchs, C AF Ogino, S. Imamura, Y. Fuchs, C. TI LINE-1 Hypomethylation and Patient Prognosis in 1253 Colorectal Cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 702 BP 170A EP 170A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301027 ER PT J AU Primiani, A Shahid, M Yilmaz, O Ferrone, CR Borger, DR Iafrate, AJ Zhu, AX Deshpande, V AF Primiani, A. Shahid, M. Yilmaz, O. Ferrone, C. R. Borger, D. R. Iafrate, A. J. Zhu, A. X. Deshpande, V. TI Microsatellite Instability in Gallbladder Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 713 BP 172A EP 173A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301038 ER PT J AU Primiani, A Nazarian, RM Linskey, K Doyle, LA Duncan, LM Odze, R Zukerberg, LR AF Primiani, A. Nazarian, R. M. Linskey, K. Doyle, L. A. Duncan, L. M. Odze, R. Zukerberg, L. R. TI CK17: An Adjunctive Marker of Invasion in Squamous Neoplastic Lesions of the Anus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womans Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 714 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301039 ER PT J AU Primiani, A Shahid, M Yilmaz, O Ferrone, CR Borger, DR Iafrate, AJ Zhu, AX Deshpande, V AF Primiani, A. Shahid, M. Yilmaz, O. Ferrone, C. R. Borger, D. R. Iafrate, A. J. Zhu, A. X. Deshpande, V. TI The PI3K/mTOR Pathway in Gallbladder Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 715 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301040 ER PT J AU Schulte, S Khor, T Hagen, C Najarian, R Lauwers, G Odze, R Srivastava, A AF Schulte, S. Khor, T. Hagen, C. Najarian, R. Lauwers, G. Odze, R. Srivastava, A. TI Long Term Outcome Study of Patients with Both Inflammatory Bowel Disease and Microscopic Colitis during the Course of Illness SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dover, NH USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 734 BP 178A EP 178A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301059 ER PT J AU Shen, J Najarian, RM Dessauvagie, B Deshpande, V Kumarasinghe, MP Hamilton, M Shahid, M Lauwers, G Odze, RD Srivastava, A AF Shen, J. Najarian, R. M. Dessauvagie, B. Deshpande, V. Kumarasinghe, M. P. Hamilton, M. Shahid, M. Lauwers, G. Odze, R. D. Srivastava, A. TI Isolated Ileitis May Be a Manifestation of Crohn's Disease, but Only in Symptomatic Patients: A Multi-Institution Study of 131 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. PathWest, Perth, WA, Australia. UWA, Perth, WA, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 738 BP 179A EP 179A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301063 ER PT J AU Tse, JY Riggi, N Ting, DT Stone, JH Rivera, M Deshpande, V AF Tse, J. Y. Riggi, N. Ting, D. T. Stone, J. H. Rivera, M. Deshpande, V. TI Diagnosis of IgG4-Related Disease: No Longer an IS(H)-Sue? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Tse, J. Y.; Riggi, N.; Ting, D. T.; Stone, J. H.; Rivera, M.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 758 BP 184A EP 184A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301083 ER PT J AU Ushiku, T Moran, CJ Lauwers, GY AF Ushiku, T. Moran, C. J. Lauwers, G. Y. TI Focally Enhanced Gastritis in Pediatric Inflammatory Bowel Disease: Patterns, Associations and Significance SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Ushiku, T.; Moran, C. J.; Lauwers, G. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 760 BP 184A EP 184A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301085 ER PT J AU Ushiku, T Ban, S Arnason, T Hishima, T Fukayama, M Lauwers, GY AF Ushiku, T. Ban, S. Arnason, T. Hishima, T. Fukayama, M. Lauwers, G. Y. TI Very Well Differentiated Gastric Cancer of Intestinal Metaplasia-Type: A Systemic Analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Tokyo, Tokyo, Japan. Saiseikai Kawaguchi Gen Hosp, Saitama, Japan. Tokyo Metropolitan Komagome Hosp, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 761 BP 185A EP 185A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301086 ER PT J AU Ananthanarayanan, V Pan, Y Kocherginsky, M Tretiakova, M Amin, MB Cheng, L Epstein, JI Grignon, DJ Hansel, DE Jimenez, RE McKenney, JK Montironi, R Oliva, E Osunkoya, AO Rao, P Reuter, VE Ro, JY Shen, SS Srigley, JR Tsuzuki, T Yao, JL Antic, T Haber, M Taxy, JB Paner, GP AF Ananthanarayanan, V. Pan, Y. Kocherginsky, M. Tretiakova, M. Amin, M. B. Cheng, L. Epstein, J. I. Grignon, D. J. Hansel, D. E. Jimenez, R. E. McKenney, J. K. Montironi, R. Oliva, E. Osunkoya, A. O. Rao, P. Reuter, V. E. Ro, J. Y. Shen, S. S. Srigley, J. R. Tsuzuki, T. Yao, J. L. Antic, T. Haber, M. Taxy, J. B. Paner, G. P. TI Influence of Histologic Criteria and Confounding Factors (CFs) in Staging Equivocal Cases for Microscopic Perivesical Tissue Invasion (MPVI or pT3a): An Interobserver Study among Expert GU Pathologists SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Chicago, Chicago, IL 60637 USA. Emory Univ, Atlanta, GA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Indiana Univ, Indianapolis, IN 46204 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Cleveland Clin, Cleveland, OH 44106 USA. Mayo Clin, Rochester, MN USA. Polytech Univ Marche Reg, Ancona, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Methodist Hosp, Houston, TX 77030 USA. McMaster Univ, Hamilton, ON, Canada. Nagoya Daini Red Cross Hosp, Nagoya, Aichi, Japan. Univ Rochester, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 802 BP 194A EP 195A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301126 ER PT J AU Dong, F Ping, Y Wang, C Wu, S Xiao, Y McDougal, WS Young, RH Wu, CL AF Dong, F. Ping, Y. Wang, C. Wu, S. Xiao, Y. McDougal, W. S. Young, R. H. Wu, C-L TI Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Dong, F.; Ping, Y.; Wang, C.; Wu, S.; Xiao, Y.; McDougal, W. S.; Young, R. H.; Wu, C-L] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 852 BP 206A EP 206A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301176 ER PT J AU Flynn, L Sheils, O O'Leary, JJ Finn, SP Watson, W Loda, M Mucci, L AF Flynn, L. Sheils, O. O'Leary, J. J. Finn, S. P. Watson, W. Loda, M. Mucci, L. TI miRNA Signatures of Indolent and Aggressive Prostate Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Dublin, Trinity Coll, Dublin, Ireland. Univ Coll Dublin, Dublin 2, Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 875 BP 211A EP 211A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301199 ER PT J AU Mason, EF Sadow, PM Wagner, AJ Remillard, SP Flood, TA Belanger, EC Hornick, JL Barletta, JA AF Mason, E. F. Sadow, P. M. Wagner, A. J. Remillard, S. P. Flood, T. A. Belanger, E. C. Hornick, J. L. Barletta, J. A. TI Identification of Succinate Dehydrogenase-Deficient Bladder Paragangliomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ottawa Hosp, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 966 BP 233A EP 233A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301290 ER PT J AU Ali, RH Kurihara, S Endo, M Rouzbahman, M Hoang, LN Melnyk, N Marino-Enriquez, A Dal Cin, P Fletcher, JA Oliva, E Huntsman, DG Oda, Y Nucci, MR Lee, CH AF Ali, R. H. Kurihara, S. Endo, M. Rouzbahman, M. Hoang, L. N. Melnyk, N. Marino-Enriquez, A. Dal Cin, P. Fletcher, J. A. Oliva, E. Huntsman, D. G. Oda, Y. Nucci, M. R. Lee, C-H TI Genetic Reclassification of Undifferentiated Endometrial Sarcoma: Clinical Relevance SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Kyushu Univ, Fukuoka 812, Japan. Univ Toronto, Toronto, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1096 BP 263A EP 263A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301421 ER PT J AU Bandyopadhyay, S Winer, I Mert, I Oliva, E Nucci, M Al-Wahab, Z Guan, H Arabi, H Alosh, B Van de Vijver, KK Ali-Fehmi, R AF Bandyopadhyay, S. Winer, I. Mert, I. Oliva, E. Nucci, M. Al-Wahab, Z. Guan, H. Arabi, H. Alosh, B. Van de Vijver, K. K. Ali-Fehmi, R. TI Clinical Significance of Lymphovascular Space Invasion in Uterine Serous Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Wayne State Univ, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. King Abdul Aziz Med City, Jeddah, Saudi Arabia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1106 BP 266A EP 266A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301431 ER PT J AU Hoang, LN McConechy, MK Koebel, M Han, G Rouzbahman, M Davidson, B Irving, J Ali, R Leung, S Oliva, E Nucci, MR Soslow, RA Huntsman, DG Gilks, CB Lee, CH AF Hoang, L. N. McConechy, M. K. Koebel, M. Han, G. Rouzbahman, M. Davidson, B. Irving, J. Ali, R. Leung, S. Oliva, E. Nucci, M. R. Soslow, R. A. Huntsman, D. G. Gilks, C. B. Lee, C-H TI Histotype-Genotype Correlation in 36 High-Grade Endometrial Carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Calgary, Calgary, AB, Canada. Univ Toronto, Toronto, ON, Canada. Norwegian Radium Hosp, Oslo, Norway. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1160 BP 278A EP 278A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301485 ER PT J AU Lee, CH Hoang, LN Reyes, C Soslow, RA Nucci, MR Oliva, E AF Lee, C-H Hoang, L. N. Reyes, C. Soslow, R. A. Nucci, M. R. Oliva, E. TI Frequent Immunohistochemical Expression of KIT in YWHAE-FAM22 Endometrial Stromal Sarcoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1192 BP 285A EP 285A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301517 ER PT J AU Zane, NA Kraft, S Faquin, W Stone, JH Deshpande, V AF Zane, N. A. Kraft, S. Faquin, W. Stone, J. H. Deshpande, V. TI IgG4-Related Disease Is a Rare Cause of Recurrent Mastoiditis and Can Be Mimicked by Severe Otitis Media SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Zane, N. A.; Kraft, S.; Faquin, W.; Stone, J. H.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1317 BP 315A EP 315A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301642 ER PT J AU Boyer, DF Lindeman, NI Harris, NL Ferry, JA AF Boyer, D. F. Lindeman, N. I. Harris, N. L. Ferry, J. A. TI Peripheral T-Cell Lymphomas with Cytotoxic Phenotype in Patients with Nodal SLL/CLL SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1341 BP 321A EP 321A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301666 ER PT J AU Chen, BJ Ouyang, J Xu, ML Yu, H Fletcher, CDM Sun, H Shipp, MA Rodig, SJ AF Chen, B. J. Ouyang, J. Xu, M. L. Yu, H. Fletcher, C. D. M. Sun, H. Shipp, M. A. Rodig, S. J. TI Expression of the Immunosuppressive Molecules PD-L1 and Galectin-1 by EBV+ Lymphoproliferative Disorders: Novel Candidates for Targeted Immunotherapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. DFCI, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. UMass Mem Hosp, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1351 BP 323A EP 323A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301676 ER PT J AU Huck, A Fathi, A Hasserjian, R AF Huck, A. Fathi, A. Hasserjian, R. TI Cytopenia Prior to AML Diagnosis Predicts Aggressive Behavior Even in the Absence of Antecedent MDS: Another Diagnostic Criterion for AML with Myelodysplasia-Related Changes? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Huck, A.; Fathi, A.; Hasserjian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1395 BP 333A EP 333A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302012 ER PT J AU Hwang, DG Dorfman, DM Briggs, DA Silverio, R Pozdnyakova, O AF Hwang, D. G. Dorfman, D. M. Briggs, D. A. Silverio, R. Pozdnyakova, O. TI Detecting Myelodysplastic Syndromes on Peripheral Blood Using a Machine Learning Approach To Analyze Multiparameter Hematology Analyzer Data SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Virginia Mason Med Ctr, Seattle, WA 98101 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1399 BP 334A EP 334A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302016 ER PT J AU Klepeis, V Hasserjian, RP AF Klepeis, V. Hasserjian, R. P. TI Refractory Anemia with Excess Blasts in Transformation Exhibits Clinicopathologic Features and Clinical Behavior Similar to AML with >= 30% Blasts SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Klepeis, V.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1410 BP 336A EP 336A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302027 ER PT J AU Klepeis, VE Zukerberg, LR Hasserjian, RP AF Klepeis, V. E. Zukerberg, L. R. Hasserjian, R. P. TI Genetic Subtypes of Acute Myeloid Leukemia Are Associated with Distinctive Features of the Bone Marrow Microenvironment SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Klepeis, V. E.; Zukerberg, L. R.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1411 BP 336A EP 337A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302028 ER PT J AU Nicolae, A Huppmann, AR Slack, GW Ferry, JA Harris, NL Pittaluga, S Jaffe, ES Hasserjian, RP AF Nicolae, A. Huppmann, A. R. Slack, G. W. Ferry, J. A. Harris, N. L. Pittaluga, S. Jaffe, E. S. Hasserjian, R. P. TI EBV Is Infrequently Expressed in the LP Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. BC Canc Agcy, Vancouver, BC, Canada. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1473 BP 352A EP 352A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302090 ER PT J AU O'Malley, DP Kim, YS Sohani, A Weiss, L Perkins, S Burke, JS Fisher, C Orazi, A AF O'Malley, D. P. Kim, Y. S. Sohani, A. Weiss, L. Perkins, S. Burke, J. S. Fisher, C. Orazi, A. TI Immunohistochemical Characterization of Vascular and Stromal Proliferations of Spleen SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Alta Bates Med Ctr, Berkeley, CA USA. Royal Marsden Hosp, London SW3 6JJ, England. Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1475 BP 352A EP 352A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302092 ER PT J AU O'Malley, DP Zuckerberg, L Smith, L Barry, TS Gunn, S Tam, W Orazi, A Kim, YS Weiss, L AF O'Malley, D. P. Zuckerberg, L. Smith, L. Barry, T. S. Gunn, S. Tam, W. Orazi, A. Kim, Y. S. Weiss, L. TI The Genetics of Interdigitating Dendritic Cell Tumors Shares Some Changes with Langerhans Cell Histiocytosis in Select Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Spectrum Pathol, Mission Viejo, CA USA. PathCentral, Irvine, CA USA. Weill Comell Med Ctr, New York, NY USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1476 BP 353A EP 353A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302093 ER PT J AU Pozdnyakova, O Shahsafaei, A Freeman, G Dorfman, D AF Pozdnyakova, O. Shahsafaei, A. Freeman, G. Dorfman, D. TI A Panel of Follicular Helper T-Cell (T-FH) Immunophenotypic Markers Identifies and Differentiates T-FH-Derived Neoplasms from Other T-Cell Neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1486 BP 355A EP 355A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302103 ER PT J AU Rogers, HJ Vardiman, JW Anastasi, J Raca, G Savage, NM Cherry, AM Arber, D Moore, E Morrissette, JJD Bagg, A Liu, YC Mathew, S Orazi, A Lin, P Wang, SA Bueso-Ramos, CE Foucar, K Hasserjian, RP Hsi, ED AF Rogers, H. J. Vardiman, J. W. Anastasi, J. Raca, G. Savage, N. M. Cherry, A. M. Arber, D. Moore, E. Morrissette, J. J. D. Bagg, A. Liu, Y-C Mathew, S. Orazi, A. Lin, P. Wang, S. A. Bueso-Ramos, C. E. Foucar, K. Hasserjian, R. P. Hsi, E. D. TI Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival in Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2); a Bone Marrow Pathology Group Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Chicago, Chicago, IL 60637 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Penn, Philadelphia, PA 19104 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1498 BP 358A EP 358A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302115 ER PT J AU Ryan, RJH Akin, C Castells, M Selig, MK Nielsen, GP Ferry, JA Hornick, JL AF Ryan, R. J. H. Akin, C. Castells, M. Selig, M. K. Nielsen, G. P. Ferry, J. A. Hornick, J. L. TI Mast Cell Sarcoma: An Aggressive and Potentially Under-Diagnosed Neoplasm That May Be Responsive to Targeted Therapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1501 BP 359A EP 359A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302118 ER PT J AU Tandon, B Swerdlow, SH Hasserjian, RP Gibson, SE AF Tandon, B. Swerdlow, S. H. Hasserjian, R. P. Gibson, S. E. TI Is Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) a Lymphoma of Mantle Zone B-Cells? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1522 BP 364A EP 364A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302139 ER PT J AU Yagi, Y Qureshi, I Malik, AZ Wilbur, DC AF Yagi, Y. Qureshi, I. Malik, A. Z. Wilbur, D. C. TI Challenges in Establishing the WSI Based Digital Pathology Facility and Telepathology Network between Pakistna and USA SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Holy Family Hosp, Rawalpindi, Pakistan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1598 BP 382A EP 383A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302214 ER PT J AU Fazlollahi, L Dias-Santagata, D Sahora, K Morales-Oyarvide, V Bernardo, LA Iafrate, AJ Pitman, MB Fernandez-del Castillo, C Mino-Kenudson, M AF Fazlollahi, L. Dias-Santagata, D. Sahora, K. Morales-Oyarvide, V. Bernardo, L. A. Iafrate, A. J. Pitman, M. B. Fernandez-del Castillo, C. Mino-Kenudson, M. TI GNAS Mutations in Concomitant Pancreatic Ductal Adenocarcinoma: A Pilot Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Fazlollahi, L.; Dias-Santagata, D.; Sahora, K.; Morales-Oyarvide, V.; Bernardo, L. A.; Iafrate, A. J.; Pitman, M. B.; Fernandez-del Castillo, C.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1765 BP 424A EP 424A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302381 ER PT J AU Shahid, M Zukerberg, LR Deshpande, V AF Shahid, M. Zukerberg, L. R. Deshpande, V. TI Is Investing AdditionalTime on Mitotic Counts in Neuroendocrine Neoplasm Clinically Relevant? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Shahid, M.; Zukerberg, L. R.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1791 BP 430A EP 430A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302407 ER PT J AU Sous, JF Sahora, K Shvetz, D Fernandez-del-Castillo, C Pitman, MB Mino-Kenudson, M AF Sous, J. F. Sahora, K. Shvetz, D. Fernandez-del-Castillo, C. Pitman, M. B. Mino-Kenudson, M. TI Protein Expression of the SWI/SNF Chromatin Remolding Subunits in Intraductal Papillary Mucinous Neoplasm (IPMN) and Pancreatic Ductal Adenocarcinoma (PDAC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Sous, J. F.; Sahora, K.; Shvetz, D.; Fernandez-del-Castillo, C.; Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1796 BP 431A EP 431A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302412 ER PT J AU Wang, JL Shvetz, D Sahora, K Fernandez-del Castillo, C Pitman, M Mino-Kenudson, M AF Wang, J. L. Shvetz, D. Sahora, K. Fernandez-del Castillo, C. Pitman, M. Mino-Kenudson, M. TI Activation of Src and STAT3 in Intraductal Papillary Mucinous Neoplasm of the Pancreas (IPMN) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1800 BP 432A EP 432A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302416 ER PT J AU Lindeman, NI MacConaill, LE Garcia, E Kuo, FC Longtine, JA Hahn, WC Kantoff, PW Rollins, BJ AF Lindeman, N. I. MacConaill, L. E. Garcia, E. Kuo, F. C. Longtine, J. A. Hahn, W. C. Kantoff, P. W. Rollins, B. J. TI Profile: Results from Multiplexed Mass Spectrometric Genotyping of 2178 Cancer Patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mt Sinai Hosp, New York, NY 10029 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1816 BP 436A EP 436A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302431 ER PT J AU Waldron, L Parmigiani, G Fuchs, C Huttenhower, C Ogino, S AF Waldron, L. Parmigiani, G. Fuchs, C. Huttenhower, C. Ogino, S. TI Expression Profiling and Molecular Classification of Colorectal Cancer: Meta-Analysis of 8 Independent mRNA Expression Datasets across the Globe SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1830 BP 439A EP 439A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302445 ER PT J AU Pessarakli, MM Phan, RT AF Pessarakli, M. M. Phan, R. T. TI Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Variants and Hyperhomocysteinemia in United States Veterans SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 USC, Keck Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1853 BP 444A EP 445A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302468 ER PT J AU Matsubara, O Miyai, K Ishikawa, V Nakatani, Y Mark, EJ AF Matsubara, O. Miyai, K. Ishikawa, V. Nakatani, Y. Mark, E. J. TI Epithelial-Mesenchymal Transition (EMT) in Active Fibroblastic Foci in IPF/UIP SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Japanese Fdn Canc Res, Inst Canc, Koto Ku, Tokyo 170, Japan. Chiba Univ, Chiba, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1911 BP 459A EP 459A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302526 ER PT J AU Miyamoto, A Sharma, A Nishino, M Mino-Kenudson, M Mark, EJ AF Miyamoto, A. Sharma, A. Nishino, M. Mino-Kenudson, M. Mark, E. J. TI Acute Exacerbation of Non-Specific Interstitial Pneumonia Compared to That of Usual Interstitial Pneumonia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Toranomon Gen Hosp, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1915 BP 460A EP 460A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302530 ER PT J AU Nishino, M Mathai, SK O'Donnell, WJ Kradin, RL AF Nishino, M. Mathai, S. K. O'Donnell, W. J. Kradin, R. L. TI Intraalveolar Fibrin Is Associated with Poor Outcomes in Cryptogenic Organizing Pneumonia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Nishino, M.; Mathai, S. K.; O'Donnell, W. J.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1921 BP 462A EP 462A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302536 ER PT J AU Setia, N Janne, PA Sholl, LM AF Setia, N. Janne, P. A. Sholl, L. M. TI Long Term Effects of EGFR Tyrosine Kinase Inhibitor Therapy on the Non-Neoplastic Lung SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1939 BP 466A EP 466A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302554 ER PT J AU Sholl, L Sun, H Ligon, A Butaney, M Janne, PA Rodig, S AF Sholl, L. Sun, H. Ligon, A. Butaney, M. Janne, P. A. Rodig, S. TI MET Copy Number by Dual Color Brightfield In Situ Hybridization and Fluorescence In Situ Hybridization Correlates with Met Protein Expression in Lung Adenocarcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1942 BP 467A EP 467A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302557 ER PT J AU Sholl, L Sun, H Butaney, M Lee, C Janne, PA Rodig, S AF Sholl, L. Sun, H. Butaney, M. Lee, C. Janne, P. A. Rodig, S. TI ROS Immunohistochemistry Is a Sensitive and Specific Tool for Detection of ROS Rearrangements in Lung Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1943 BP 467A EP 467A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302558 ER PT J AU Ackerley, EJ Cavan, AE Wilson, PL Berbeco, RI Meyer, J AF Ackerley, E. J. Cavan, A. E. Wilson, P. L. Berbeco, R. I. Meyer, J. TI Application of a spring-dashpot system to clinical lung tumor motion data SO MEDICAL PHYSICS LA English DT Article DE spring-dashpot model; radiotherapy; lung tumor modeling; respiration; differential equation ID REAL-TIME; TRACKING SYSTEM; RESPIRATORY MOTION; GATED RADIOTHERAPY; COMPENSATION; MOVEMENT; FEASIBILITY; SURROGATES; PREDICTION; LOCATION AB Purpose: The treatment efficacy of radiation therapy for lung tumors can be increased by compensating for breath-induced tumor motion. In this study, we quantitatively examine a mathematical model of pseudomechanical linkages between an external surrogate signal and lung tumor motion. Methods: A spring-dashpot system based on the Voigt model was developed to model the correlation between abdominal respiratory motion and tumor motion during lung radiotherapy. The model was applied to clinical data obtained from 52 treatments ("beams") from 10 patients, treated on the Mitsubishi Real-Time Radiation Therapy system, Sapporo, Japan. In Stage 1, model parameters were optimized for individual patients and beams to determine reference values and to investigate how well the model can describe the data. In Stage 2, for each patient the optimal parameters determined for a single beam were applied to data from other beams to investigate whether a beam-specific set of model parameters is sufficient to model tumor motion over a course of treatment. Results: In Stage 1, the baseline root mean square (RMS) residual error for all individually optimized beam data was 0.90 +/- 0.40 mm (mean +/- 1 standard deviation). In Stage 2, patient-specific model parameters based on a single beam were found to model the tumor position closely, even for irregular beam data, with a mean increase with respect to Stage 1 values in RMS error of 0.37 mm. On average, the obtained model output for the tumor position was 95% of the time within an absolute bound of 2.0 and 2.6 mm in Stages 1 and 2, respectively. The model was capable of dealing with baseline, amplitude and frequency variations of the input data, as well as phase shifts between the input abdominal and output tumor signals. Conclusions: These results indicate that it may be feasible to collect patient-specific model parameters during or prior to the first treatment, and then retain these for the rest of the treatment period. The model has potential for clinical application during radiotherapy treatment of lung tumors. (c) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4788643] C1 [Ackerley, E. J.; Wilson, P. L.] Univ Canterbury, Dept Math & Stat, Christchurch 8140, New Zealand. [Cavan, A. E.; Meyer, J.] Univ Canterbury, Dept Phys & Astron, Christchurch 8140, New Zealand. [Cavan, A. E.] Christchurch Hosp, Dept Med Phys & Bioengn, Christchurch, New Zealand. [Berbeco, R. I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Berbeco, R. I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyer, J.] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. RP Wilson, PL (reprint author), Univ Canterbury, Dept Math & Stat, Private Bag 4800, Christchurch 8140, New Zealand. EM phillip.wilson@canterbury.ac.nz OI Meyer, Juergen/0000-0003-4350-2222 FU Canterbury Medical Research Foundation FX The authors would like to thank Dr. Seiko Nishioka and Dr. Hiroki Shirato, for the clinical data provided from the Nippon Telegraph and Telephone Corporation Hospital in Sapporo, Japan. Thanks also to the Canterbury Medical Research Foundation for financial support for Alicia Cavan. NR 38 TC 2 Z9 2 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2013 VL 40 IS 2 AR 021713 DI 10.1118/1.4788643 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086YZ UT WOS:000314727700017 PM 23387736 ER PT J AU Zygmanski, P Hoegele, W Tsiamas, P Cifter, F Ngwa, W Berbeco, R Makrigiorgos, M Sajo, E AF Zygmanski, Piotr Hoegele, Wolfgang Tsiamas, Panagiotis Cifter, Fulya Ngwa, Wil Berbeco, Ross Makrigiorgos, Mike Sajo, Erno TI A stochastic model of cell survival for high-Z nanoparticle radiotherapy SO MEDICAL PHYSICS LA English DT Article DE gold; nanoparticle; LEM; RBE ID LOCAL EFFECT MODEL; MONTE-CARLO-SIMULATION; GOLD NANOPARTICLES; DOSE ENHANCEMENT; RADIATION-THERAPY; CLINICAL SCENARIO; MAMMALIAN-CELLS; PHOTON ENERGY; X-RAY; DNA AB Purpose: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. Methods: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. Results: The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. Conclusions: The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies. c 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4773885] C1 [Zygmanski, Piotr; Tsiamas, Panagiotis; Ngwa, Wil; Berbeco, Ross; Makrigiorgos, Mike] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zygmanski, Piotr; Tsiamas, Panagiotis; Ngwa, Wil; Berbeco, Ross; Makrigiorgos, Mike] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hoegele, Wolfgang] Univ Regensburg, Dept Radiat Oncol, D-93053 Regensburg, Germany. [Cifter, Fulya; Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pzygmanski@lroc.harvard.edu RI Hoegele, Wolfgang/A-2575-2013 OI Hoegele, Wolfgang/0000-0002-5303-9334 NR 47 TC 6 Z9 6 U1 0 U2 19 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2013 VL 40 IS 2 AR 024102 DI 10.1118/1.4773885 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086YZ UT WOS:000314727700062 PM 23387781 ER PT J AU Galanakos, SP Zoubos, AB Mourouzis, I Ignatiadis, I Bot, AGJ Soucacos, PN AF Galanakos, Spyridon P. Zoubos, Aristides B. Mourouzis, Iordanis Ignatiadis, Ioannis Bot, Arjan G. J. Soucacos, Panayotis N. TI Prognostic scoring system for peripheral nerve repair in the upper extremity SO MICROSURGERY LA English DT Article ID FUNCTIONAL ASSESSMENT; INJURIES; ULNAR; HAND; SURGERY; OUTCOMES; PREDICTORS; RECOVERY; FOREARM; TRAUMA AB So far, predictive models with individualized estimates of prognosis for patients with peripheral nerve injuries are lacking. Our group has previously shown the prognostic value of a standardized scoring system by examining the functional outcome after acute, sharp complete laceration and repair of median and/or ulnar nerves at various levels in the forearm. In the present study, we further explore the potential mathematical model in order to devise an effective prognostic scoring system. We retrospectively collected medical record data of 73 cases with a peripheral nerve injury in the upper extremity in order to estimate which patients would return to work, and what time was necessary to return to the pre-injury work. Postoperative assessment followed the protocol described by Rosen and Lundborg. We found that return to pre-injury work can be predicted with high sensitivity (100%) and specificity (95%) using the total numerical score of the Rosen and Lundborg protocol at the third follow-up interval (TS3) as well as the difference between the TS3 and the total score at second follow-up interval (TS2). In addition, the factors age and type of injured nerve (median, ulnar, or combined) can determine the time of return to work based on a mathematical model. This prognostic protocol can be a useful tool to provide information about the functional and social prospects of the patients with these types of injuries. (c) 2012 Wiley Periodicals, Inc. Microsurgery, 2013. C1 [Galanakos, Spyridon P.; Zoubos, Aristides B.; Mourouzis, Iordanis; Ignatiadis, Ioannis; Soucacos, Panayotis N.] Univ Athens, Dept Orthopaed Surg 1, ATTIKON Univ Hosp, Athens 12462, Greece. [Bot, Arjan G. J.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Galanakos, SP (reprint author), Univ Athens, Dept Orthopaed Surg 1, ATTIKON Univ Hosp, 1 Rimini St, Athens 12462, Greece. EM spyros_galanakos@yahoo.gr NR 33 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0738-1085 J9 MICROSURG JI Microsurgery PD FEB PY 2013 VL 33 IS 2 BP 105 EP 111 DI 10.1002/micr.22000 PG 7 WC Surgery SC Surgery GA 089GH UT WOS:000314898400003 PM 22707451 ER PT J AU Yang, XY Kallarakal, A Saptharishi, N Jiang, HG Yang, ZW Xie, YQ Mitra, G Zheng, XX Strom, TB Soman, G AF Yang, Xiaoyi Kallarakal, Abraham Saptharishi, Nirmala Jiang, Hengguang Yang, Zhiwen Xie, Yueqing Mitra, George Zheng, Xin Xiao Strom, Terry B. Soman, Gopalan TI Molecular Characterization and Functional Activity of an IL-15 Antagonist MutIL-15/Fc Human Fusion Protein SO MOLECULAR PHARMACEUTICS LA English DT Article DE fusion protein; bioactivity; SEC-MALS; N-glycoprofiling; Fc receptor binding; surface plasmon resonance ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SENSITIVE FLUORESCENCE DETECTION; T-CELLS; QUANTITATIVE-DETERMINATION; MONOCLONAL-ANTIBODIES; THERAPEUTIC PROTEINS; GROWTH-FACTOR; FC DOMAIN; RECEPTOR; INTERLEUKIN-15 AB Fc fusion proteins are a new emerging class of molecules for immune-targeted delivery of therapeutic proteins. Biophysical and bioanalytical characterization is critical for clinical development and delivery of therapeutic proteins. Here we report molecular and functional characterization of a recombinant human fusion protein Mutant IL-15/Fc. MutIL-15/Fc has a molecular weight of similar to 95 kDa as determined by multiangle laser light scattering with online size exclusion chromatography and migrated at a faster rate (lower retention time) in gel filtration column. The kinetics of binding of MutIL-15/Fc to Fc gamma receptor is best fitted in a bivalent modal with K-D1 5 mu M and K-D2 9 mu M determined by surface plasmon resonance (BIAcore). N-Glycoprofiling analysis revealed extensive glycosylation of MutIL-15/Fc. The Fc and IL-15 components in the MutIL-15/Fc are detected using the dual mode ELISA. The HT-2 cell proliferation inhibition assay is qualified as a quantitative in vitro marker functional assay. Molecular state changes associated with forced stress analyzed by SEC-MALS resulted in changes in bioactivity and Fc:Fc gamma receptor interaction affinity. These data provide a systematic approach to molecular and functional characterization of the MutIL-15/Fc to establish product consistency and stability monitoring during storage and under drug delivery conditions. C1 [Yang, Xiaoyi; Kallarakal, Abraham; Saptharishi, Nirmala; Jiang, Hengguang; Yang, Zhiwen; Xie, Yueqing; Mitra, George; Soman, Gopalan] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Zheng, Xin Xiao] Univ Pittsburgh, Med Ctr, Thomas Starzl Transplant Inst, Pittsburgh, PA 15261 USA. [Strom, Terry B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Med Sch,Dept Surg & Med,Transplant Inst, Boston, MA 02215 USA. RP Soman, G (reprint author), SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM somang@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIDDK; NIAID; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and funding from NIDDK and NIAID. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. Our sincere thanks are due to Drs. Jason Yovandich and Stephen P. Creekmore of the Biological Resources Branch, DTP, NCI for the support of this work and review of this manuscript. We would like to acknowledge the technical support from Dr. Hong Chen during the early stages of this work. Mr. Trevor Broadt of Process Analytics is acknowledged for helpful review of the manuscript. The support and encouragement from Dr. Steve Giardina and the process analytics staff are also acknowledged. Thanks are also due to Dr. Jianwei Zhu of Early Stage Process Development in BDP. NR 41 TC 0 Z9 0 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD FEB PY 2013 VL 10 IS 2 BP 717 EP 727 DI 10.1021/mp300513j PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 085PT UT WOS:000314627400031 PM 23311475 ER PT J AU Tremblay, JP Xiao, X Aartsma-Rus, A Barbas, C Blaus, HM Bogdanove, AJ Boycott, K Brauns, S Breakefield, XO Bueren, JA Buschmann, M Byrne, BJ Calos, M Cathomen, T Chamberlain, J Chuah, M Cornetta, K Davies, KE Dickson, JG Duchateau, P Flotte, TR Gaudet, D Gersbach, CA Gilbert, R Glorioso, J Herzog, RW High, KA Huang, WL Huard, J Joung, JK Liu, DP Liu, DX Lochmuller, H Lustig, L Martens, J Massie, B Mavilio, F Mendell, JR Nathwani, A Ponder, K Porteus, M Puymirat, J Samulski, J Takeda, S Thrasher, A VandenDriessche, T Wei, YQ Wilson, JM Wilton, SD Wolfe, JH Gao, GP AF Tremblay, Jacques P. Xiao, Xiao Aartsma-Rus, Annemieke Barbas, Carlos Blaus, Helen M. Bogdanove, Adam J. Boycott, Kym Brauns, Serge Breakefield, Xandra O. Bueren, Juan A. Buschmann, Michael Byrne, Barry J. Calos, Michele Cathomen, Toni Chamberlain, Jeffrey Chuah, Marinee Cornetta, Kenneth Davies, Kay E. Dickson, J. George Duchateau, Philippe Flotte, Terence R. Gaudet, Daniel Gersbach, Charles A. Gilbert, Renald Glorioso, Joseph Herzog, Roland W. High, Katherine A. Huang, Wenlin Huard, Johnny Joung, J. Keith Liu, Depei Liu, Dexi Lochmueller, Hanns Lustig, Lawrence Martens, Jeffrey Massie, Bernard Mavilio, Fulvio Mendell, Jerry R. Nathwani, Amit Ponder, Katherine Porteus, Matthew Puymirat, Jack Samulski, Jude Takeda, Shin'ichi Thrasher, Adrian VandenDriessche, Thierry Wei, Yuquan Wilson, James M. Wilton, Steve D. Wolfe, John H. Gao, Guangping TI Translating the Genomics Revolution: The Need for an International Gene Therapy Consortium for Monogenic Diseases SO MOLECULAR THERAPY LA English DT Letter C1 [Tremblay, Jacques P.; Puymirat, Jack] Univ Laval, Ctr Rech CHU, Quebec City, PQ, Canada. [Tremblay, Jacques P.; Puymirat, Jack] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada. [Xiao, Xiao] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Aartsma-Rus, Annemieke] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Barbas, Carlos] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Barbas, Carlos] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Barbas, Carlos] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Blaus, Helen M.] Stanford Univ, Sch Med, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA. [Bogdanove, Adam J.] Cornell Univ, Dept Plant Pathol & Plant Microbe Biol, Ithaca, NY USA. [Boycott, Kym] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada. [Brauns, Serge] AFM Telethon, Paris, France. [Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Bueren, Juan A.] Ctr Invest Energet Medioambientales & Tecnol, Hematopoiet Innovat Therapies Div, Madrid, Spain. [Bueren, Juan A.] Ctr Invest Red Enfermedades Raras CIEMAT CIBERER, Madrid, Spain. [Buschmann, Michael] Ecole Polytech, Dept Chem Engn, Montreal, PQ H3C 3A7, Canada. [Buschmann, Michael] Ecole Polytech, Inst Biomed Engn, Montreal, PQ H3C 3A7, Canada. [Byrne, Barry J.; Herzog, Roland W.] Univ Florida, Dept Pediat, Gainesville, FL USA. [Calos, Michele] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Cathomen, Toni] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Lab Cell & Gene Therapy, Freiburg, Germany. [Chamberlain, Jeffrey] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Chamberlain, Jeffrey] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Chamberlain, Jeffrey] Univ Washington, Sch Med, Dept Biochem, Seattle, WA 98195 USA. [Chuah, Marinee; VandenDriessche, Thierry] Vrije Univ Brussel, Dept Gene Therapy & Regenerat Med, Louvain, Belgium. [Chuah, Marinee; VandenDriessche, Thierry] Katholieke Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Louvain, Belgium. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Davies, Kay E.] Univ Oxford, MRC Funct Genom Unit, Oxford, England. [Dickson, J. George] Royal Holloway Univ London, Sch Biol Sci, Egham, Surrey, England. [Duchateau, Philippe] Cellectis, Paris, France. [Flotte, Terence R.] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA USA. [Flotte, Terence R.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Gaudet, Daniel] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Gersbach, Charles A.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Gersbach, Charles A.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA. [Gilbert, Renald; Massie, Bernard] Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. [Glorioso, Joseph] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [High, Katherine A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [High, Katherine A.] Childrens Hosp Philadelphia, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Huang, Wenlin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China. [Huard, Johnny] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA USA. [Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Liu, Depei] Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Dept Biochem & Mol Biol, Beijing 100730, Peoples R China. [Liu, Depei] Peking Union Med Coll, Beijing 100021, Peoples R China. [Liu, Dexi] Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. [Lochmueller, Hanns] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Lustig, Lawrence] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. [Martens, Jeffrey] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Mavilio, Fulvio] Genethon, Evry, France. [Mendell, Jerry R.] Nationwide Childrens Hosp, Paul D Wellstone Ctr, Columbus, OH USA. [Mendell, Jerry R.] Ohio State Univ, Columbus, OH 43210 USA. [Nathwani, Amit] UCL Canc Inst, Dept Haematol, London, England. [Ponder, Katherine] Washington Univ, Dept Internal Med, St Louis, MO USA. [Porteus, Matthew] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Samulski, Jude] Duke Univ, Med Ctr, Dept Surg, Cardiothorac Div, Durham, NC 27710 USA. [Takeda, Shin'ichi] Natl Ctr Neurol & Psychiat, Tokyo, Japan. [Thrasher, Adrian] UCL Inst Child Hlth, London, England. [Wei, Yuquan] Natl Key Lab Biotherapy, Natl Gene Therapy Program, Chengdu, Peoples R China. [Wei, Yuquan] Sichuan Univ, Chengdu 610064, Peoples R China. [Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Wilton, Steve D.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Crawley, WA, Australia. [Wolfe, John H.] Univ Penn, Philadelphia, PA 19104 USA. [Wolfe, John H.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gao, Guangping] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Tremblay, JP (reprint author), Univ Laval, Ctr Rech CHU, Quebec City, PQ, Canada. EM Jacques-P.Tremblay@crchul.ulaval.ca RI MAVILIO, Fulvio/J-6125-2013; Bueren, Juan/L-6112-2014; Wilson, James/F-9220-2011; OI Bueren, Juan/0000-0002-3228-7013; Wilson, James/0000-0002-9630-3131; Lochmuller, Hanns/0000-0003-2324-8001; Buschmann, Michael/0000-0002-2242-6198; Mavilio, Fulvio/0000-0003-0459-4320; Cathomen, Toni/0000-0002-7757-4630 FU Howard Hughes Medical Institute; Medical Research Council [G0801763, G0902219, MC_UU_12021/2, MR/K000608/1]; NCATS NIH HHS [UL1 TR000161]; NHLBI NIH HHS [P40 HL116242]; NIAMS NIH HHS [R01 AR040864, R01 AR056394]; NIDDK NIH HHS [P30 DK079312]; NIH HHS [P40 OD010939]; Wellcome Trust [090233] NR 4 TC 9 Z9 9 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2013 VL 21 IS 2 BP 266 EP 268 DI 10.1038/mt.2013.4 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 083AH UT WOS:000314434600002 PM 23369965 ER PT J AU Goldberg, MS Hook, SS Wang, AZ Bulte, JWM Patri, AK Uckun, FM Cryns, VL Hanes, J Akin, D Hall, JB Gharkholo, N Mumper, RJ AF Goldberg, Michael S. Hook, Sara S. Wang, Andrew Z. Bulte, Jeff W. M. Patri, Anil K. Uckun, Fatih M. Cryns, Vincent L. Hanes, Justin Akin, Demir Hall, Jennifer B. Gharkholo, Nastaran Mumper, Russell J. TI Biotargeted nanomedicines for cancer: six tenets before you begin SO NANOMEDICINE LA English DT Article DE cost-effectiveness analysis; good manufacturing practice; ligand; nanoparticle; receptor targeted ID IN-VITRO; NANOPARTICLE INTERACTION; DELIVERY-SYSTEM; DRUG-RELEASE; THERAPY; BIODISTRIBUTION; TUMORS; VIVO; CONJUGATION; BIOMARKERS AB Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the 'magic bullet' that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute's Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice. C1 [Goldberg, Michael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Hook, Sara S.] NCI, Ctr Strateg Sci Initiat, Off Director, NIH, Bethesda, MD 20892 USA. [Wang, Andrew Z.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27514 USA. [Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. [Patri, Anil K.; Hall, Jennifer B.] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. [Uckun, Fatih M.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Uckun, Fatih M.] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90033 USA. [Cryns, Vincent L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Akin, Demir] Stanford Univ, Sch Med, Dept Radiol, Palo Alto, CA 94305 USA. [Gharkholo, Nastaran; Mumper, Russell J.] Univ N Carolina, UNC Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Div Mol Pharmaceut, Chapel Hill, NC 27514 USA. RP Mumper, RJ (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Div Mol Pharmaceut, Chapel Hill, NC 27514 USA. EM mumper@email.unc.edu RI Bulte, Jeff/A-3240-2008; Wang, Andrew /F-9719-2011; Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Bulte, Jeff/0000-0003-1202-1610; Wang, Andrew/0000-0002-9781-4494 FU National Cancer Institute (NCI)-NIH [HHSN261200800001E]; NCI Alliance for Nanotechnology in Cancer; Center of Cancer Nanotechnology Excellence FX This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI)-NIH under contract number HHSN261200800001E. All authors are part of the NCI Alliance for Nanotechnology in Cancer and hold either Center of Cancer Nanotechnology Excellence or Cancer Nanotechnology Platform Partnership grants. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 63 TC 16 Z9 16 U1 1 U2 76 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD FEB PY 2013 VL 8 IS 2 BP 299 EP 308 DI 10.2217/NNM.13.3 PG 10 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 087VD UT WOS:000314791200022 PM 23394158 ER PT J AU Torosean, S Flynn, B Axelsson, J Gunn, J Samkoe, KS Hasan, T Doyley, MM Pogue, BW AF Torosean, Sason Flynn, Brendan Axelsson, Johan Gunn, Jason Samkoe, Kimberley S. Hasan, Tayyaba Doyley, Marvin M. Pogue, Brian W. TI Nanoparticle uptake in tumors is mediated by the interplay of vascular and collagen density with interstitial pressure SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Fluorescence; Pressure; Collagen; Cancer; Microenvironment ID EXTRACELLULAR-MATRIX; SOLID TUMORS; FLUID PRESSURE; DRUG-DELIVERY; BREAST-CANCER; TRANSPORT; HYPERTENSION; GROWTH; CONVECTION AB Nanoparticle delivery into solid tumors is affected by vessel density, interstitial fluid pressure (IFP) and collagen, as shown in this article by contrasting the in vivo macroscopic quantitative uptake of 40 nm fluorescent beads in three tumor types. The fluorescence uptake was quantified on individual animals by normalization with the transmitted light and then normalized to normal tissue uptake in each mouse. Mean data for uptake in individual tumor lines then showed expected trends with the largest uptake in the most vascularized tumor line. Tumor lines with increased collagen were also consistent with highest interstitial fluid pressure and correlated with lowest uptake of nanoparticles. The data is consistent with a delivery model indicating that while vascular permeability is maximized by neovascular growth, it is inhibited by collagen content and the resulting interstitial pressure. Imaging of these parameters in vivo can lead to better individual noninvasive methods to assess drug penetration in situ. C1 [Torosean, Sason; Pogue, Brian W.] Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA. [Flynn, Brendan; Axelsson, Johan; Gunn, Jason; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Geisel Sch Med Dartmouth, Dept Surg, Lebanon, NH USA. [Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doyley, Marvin M.] Univ Rochester, Dept Elect & Comp Engn, Rochester, NY USA. RP Pogue, BW (reprint author), 14 Engn Dr, Hanover, NH 03755 USA. EM brian.w.pogue@dartmouth.edu RI Doyley, Marvin/N-3765-2013 FU NIH [PO1CA084203, RO1CA109558, RO1CA156177, R01CA10998] FX This work has been financially supported by NIH research grants PO1CA084203, RO1CA109558, RO1CA156177 and R01CA10998. NR 42 TC 20 Z9 20 U1 2 U2 43 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD FEB PY 2013 VL 9 IS 2 BP 151 EP 158 DI 10.1016/j.nano.2012.07.002 PG 8 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 088YL UT WOS:000314873700001 PM 22841910 ER PT J AU Waldman, E Wolfe, J AF Waldman, Elisha Wolfe, Joanne TI Palliative care for children with cancer SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID OF-LIFE CARE; PEDIATRIC ONCOLOGY; YOUNG-ADULTS; INCURABLE CANCER; DECISION-MAKING; ALTERNATIVE THERAPIES; HEALTH-PROFESSIONALS; DEVELOPING-COUNTRIES; CLINICAL ONCOLOGY; AMERICAN SOCIETY AB Over the past two decades, paediatric palliative care has emerged as both a primary approach and as its own medical subspecialty, the overall aim of which is to ease suffering for children with life-threatening illness and their families through a concurrent model of care. However, most discussions have been focused on the transition to palliative care when no realistic hope for cure exists. We believe that, because the course of cancer is so unpredictable, this idea is misleading. Indeed, palliative care is increasingly being recognized as being about not just how to cope with the process of dying, but also about how to engage in living when faced with a life-threatening illness. This article will examine our current understanding of several areas of palliative care, with the ultimate message that palliative care is simply a novel term for the total care of a child and family, an approach that should be applied consistently and concurrently regardless of disease status. By improving familiarity with palliative care and building relationships with palliative care specialists, the paediatric oncology clinician will ensure that the best care possible for children and families is provided, regardless of outcome. Waldman, E. & Wolfe, J. Nat. Rev. Clin. Oncol. 10,100-107 (2013); published online 22 January 2013; doi:10.1038/nrclinonc.2012.238 C1 [Waldman, Elisha; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu NR 97 TC 16 Z9 17 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD FEB PY 2013 VL 10 IS 2 BP 100 EP 107 DI 10.1038/nrclinonc.2012.238 PG 8 WC Oncology SC Oncology GA 088TF UT WOS:000314859300009 PM 23337915 ER PT J AU Wechsler, LR Tsao, JW Levine, SR Swain-Eng, RJ Adams, RJ Demaerschalk, BM Hess, DC Moro, E Schwamm, LH Steffensen, S Stern, BJ Zuckerman, SJ Bhattacharya, P Davis, LE Yurkiewicz, IR Alphonso, AL AF Wechsler, Lawrence R. Tsao, Jack W. Levine, Steven R. Swain-Eng, Rebecca J. Adams, Robert J. Demaerschalk, Bart M. Hess, David C. Moro, Elena Schwamm, Lee H. Steffensen, Steve Stern, Barney J. Zuckerman, Steven J. Bhattacharya, Pratik Davis, Larry E. Yurkiewicz, Ilana R. Alphonso, Aimee L. TI Teleneurology applications Report of the Telemedicine Work Group of the American Academy of Neurology SO NEUROLOGY LA English DT Article ID DEEP BRAIN-STIMULATION; ACUTE STROKE; COST-ANALYSIS; CARE; TELESTROKE; FEASIBILITY; EXPERIENCE; TELEPHONE AB Objective: To review current literature on neurology telemedicine and to discuss its application to patient care, neurology practice, military medicine, and current federal policy. Methods: Review of practice models and published literature on primary studies of the efficacy of neurology telemedicine. Results: Teleneurology is of greatest benefit to populations with restricted access to general and subspecialty neurologic care in rural areas, those with limited mobility, and those deployed by the military. Through the use of real-time audio-visual interaction, imaging, and store-and-forward systems, a greater proportion of neurologists are able to meet the demand for specialty care in underserved communities, decrease the response time for acute stroke assessment, and expand the collaboration between primary care physicians, neurologists, and other disciplines. The American Stroke Association has developed a defined policy on teleneurology, and the American Academy of Neurology and federal health care policy are beginning to follow suit. Conclusions: Teleneurology is an effective tool for the rapid evaluation of patients in remote locations requiring neurologic care. These underserved locations include geographically isolated rural areas as well as urban cores with insufficient available neurology specialists. With this technology, neurologists will be better able to meet the burgeoning demand for access to neurologic care in an era of declining availability. An increase in physician awareness and support at the federal and state level is necessary to facilitate expansion of telemedicine into further areas of neurology. Neurology (R) 2013;80:670-676 C1 [Wechsler, Lawrence R.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Tsao, Jack W.] USN, Bur Med & Surg, Falls Church, VA USA. [Levine, Steven R.] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Levine, Steven R.] Suny Downstate Med Ctr, Downstate Stroke Ctr, Brooklyn, NY 11203 USA. [Swain-Eng, Rebecca J.] Amer Acad Neurol, Minneapolis, MN USA. [Adams, Robert J.] Med Univ S Carolina, Stroke Ctr, Charleston, SC USA. [Demaerschalk, Bart M.] Mayo Clin, Dept Neurol, Phoenix, AZ USA. [Hess, David C.] Georgia Hlth Sci Univ, Augusta, GA USA. [Moro, Elena] Univ Toronto, Toronto Western Hosp, Div Neurol, Movement Disorders Ctr,UHN, Toronto, ON M5T 2S8, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Steffensen, Steve] Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA. [Stern, Barney J.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. [Zuckerman, Steven J.] Neurol Inst, Baton Rouge, LA USA. [Bhattacharya, Pratik] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Davis, Larry E.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Yurkiewicz, Ilana R.] Harvard Univ, Sch Med, Boston, MA USA. [Alphonso, Aimee L.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. RP Wechsler, LR (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU Telemedicine; Advanced Technology Research Center, United States Army; NIH; Arizona Department of Health Services; Athersys, Inc.; Lundbeck; St. Jude Medical; Medtronic; Remedy Pharmaceuticals FX L. Wechsler has served as a consultant for Abbott Vascular, Lunbeck, and Ferrer; is on the Data and Safety Monitoring Board for DIAS 3/4/J and the steering committee for CLOSURE, ACT I; and owns stock in Neurointerventional Therapeutics. J. Tsao has received funding from the Telemedicine and Advanced Technology Research Center, United States Army, to develop a military neurology telemedicine system. S. Levine has given expert review and testimony on medical legal cases and has received research funding from the NIH. R. Swain-Eng is a full-time employee of the American Academy of Neurology. R. J. Adams is cofounder of REACHCall Inc., a for-profit telemedicine platform provider. He is also a co-owner of the company with <5% of outstanding stock. He is employed by Medical University of South Carolina, which offers telestroke consultation for fair market value to hospitals in South Carolina. He also is a speaker for Genentech, which makes tPA, but owns no stock. B. Demaerschalk has received telemedicine research grant funding from the Arizona Department of Health Services. Dr. Hess is a cofounder of REACHCall Inc., a for-profit telemedicine platform provider. He is also a co-owner of the company with <5% of outstanding stock. He is employed by Georgia Health Sciences University, which offers telestroke consultation for fair market value to hospitals in Georgia. He also has research contracts with Athersys, Inc., and Lundbeck. E. Moro has received honoraria from Medtronic for consulting services and speaking. She has received research grant support from St. Jude Medical and educational grants from Medtronic and St. Jude Medical. L. Schwamm serves as a consultant to LifeImage, a teleradiology company, and on the International Steering Committee for the DIAS3/4 trial. His employer, The Massachusetts General Hospital, offers an array of telehealth services at fair market value to many area hospitals, including telestroke. He has also given expert review and testimony on medical legal cases and has received research funding from the NIH on thrombolysis and HRSA on telemedicine. S. Steffensen reports no disclosures. B. Stern has received research support from Remedy Pharmaceuticals per patient research costs and research grants from the NIH. He has also received compensation for expert witness testimony. S. Zuckerman and P. Bhattacharya report no disclosures. L. Davis is a part of the VA Teleneurology group for which the VA pays part of the research costs for the nursing staff. I. Yurkiewicz and A. Alphonso report no disclosures. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy, the Department of Defense, or the Department of Veterans Affairs. Go to Neurology.org for full disclosures. NR 39 TC 28 Z9 28 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 7 BP 670 EP 676 DI 10.1212/WNL.0b013e3182823361 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 088ZY UT WOS:000314878500015 PM 23400317 ER PT J AU Greenberg, SM AF Greenberg, Steven M. TI Stroke after Alzheimer disease I have more bad news SO NEUROLOGY LA English DT Editorial Material ID DEMENTIA; RISK; INFARCTS C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. EM sgreenberg@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 8 BP 695 EP 696 DI 10.1212/WNL.0b013e3182825196 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 092ZN UT WOS:000315161600005 PM 23303845 ER PT J AU Kimberly, WT Lima, FO O'Connor, S Furie, KL AF Kimberly, W. Taylor Lima, Fabricio O. O'Connor, Sydney Furie, Karen L. TI Sex differences and hemoglobin levels in relation to stroke outcomes SO NEUROLOGY LA English DT Article ID ISCHEMIC-STROKE; CLINICAL PRESENTATION; CEREBRAL-ISCHEMIA; BLOOD-VISCOSITY; REGISTRY; CARE; AGE; HYPERGLYCEMIA; EPIDEMIOLOGY; VALIDATION AB Objective: Women have worse outcomes after stroke compared to men. Since women have lower hemoglobin values, we examined whether hemoglobin levels may associate with worse stroke outcomes in women. Methods: We retrospectively studied 274 patients enrolled in a prospective multicenter study. We explored the relationship of hemoglobin with clinical outcome at 6 months, as measured by the modified Rankin Scale (mRS). Ordinal logistic regression was used to evaluate the independent effect of hemoglobin on clinical outcome, and to explore the influence of sex on that association. Results: Women had a lower mean hemoglobin level (11.7 +/- 1.8 g/dL) compared to men (13.3 +/- 1.7 g/dL). Low hemoglobin was associated with worse 6-month mRS outcomes in univariate analysis (p < 0.001). Lower hemoglobin remained independently associated with poor outcome after adjustment for comorbid disease, stroke severity, age, and sex. The inclusion of hemoglobin in the model attenuated the independent effect of sex on outcome. Conclusions: Sex differences in stroke outcome are linked to lower hemoglobin level, which is more prevalent in women. Further examination of this potentially modifiable predictor is warranted. Neurology (R) 2013;80:719-724 C1 [Kimberly, W. Taylor; Lima, Fabricio O.; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA. [Kimberly, W. Taylor; O'Connor, Sydney] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Div Neurocrit Care & Emerg, Boston, MA 02115 USA. RP Kimberly, WT (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA. EM wtkimberly@partners.org FU American Academy of Neurology Foundation; Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard Medical School; Pfizer Inc.; Merck Co.; NIH [1K23NS076597, 5P50NS051343-07, 1R01 NS064905-01A1, 1K23NS076597-01, 5P50 NS051343-07]; [R01HS011392-01A2] FX Supported by American Academy of Neurology Foundation clinical training research fellowship (W. T. K.), the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard Medical School, in collaboration with Pfizer Inc. and Merck & Co. (W. T. K.), and by NIH 1K23NS076597 (W. T. K.) and NIH 5P50NS051343-07 and 1R01 NS064905-01A1 (K. L. F.). The original STOPStroke study was sponsored by R01HS011392-01A2.; W.T. Kimberly reports funding from American Academy of Neurology Foundation clinical training research fellowship, the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard Medical School, in collaboration with Pfizer Inc. and Merck & Co., and by NIH 1K23NS076597-01. F. Lima reports a fellowship funded by 5P50 NS051343-07. S. O'Connor reports no disclosures. K. Furie reports funding by 5P50 NS051343-07 and 1R01 NS064905-01A1. Go to Neurology.org for full disclosures. NR 32 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 8 BP 719 EP 724 DI 10.1212/WNL.0b013e31828250ff PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 092ZN UT WOS:000315161600010 PM 23365064 ER PT J AU Zhang, Z Zhang, L Yang, X Li, Y Duan, Z AF Zhang, Z. Zhang, L. Yang, X. Li, Y. Duan, Z. TI Construction and validation of a placental tissue microarray from specimens of well-documented preeclampsia patients SO PLACENTA LA English DT Article DE Tissue microarray; Preeclampsia; Villous cytotrophoblast; Extravillous cytotrophoblast ID EXTRAVILLOUS TROPHOBLASTS; HODGKINS LYMPHOMA; G EXPRESSION; INVASIVENESS; TECHNOLOGY; CANCER; STAT3; FETAL AB Construction of tissue microarray (TMA) to validate the very large number of molecular targets of gene microarray data may provide a high throughput approach in preeclampsia study. However, the intricate structure of the placenta has limited this technique's application. In this study, 80 preeclampsia and 58 normal placental specimens were selected for constructing TMA from 400 donor block according to strict criteria. Each specimen with enough tissue area was punched 3 cores (0.6 mm in diameter each). Two pathologists marked the representative area exactly on H&E stained slide of each donor block. Then, the target tissues on the donor block were marked carefully along with the marked area on the slide. The TMA of preeclampsia were successfully constructed. H&E staining showed 98.97% (97/98) of villous cytotrophoblast (VCT) samples and 86.36% (76/88) of extravillous cytotrophoblast (EVCT) samples retained target tissue in TMA. In all cores, the area stained positive for cytokeratin was negative for vimentin, which is the characteristic of cytotrophoblast. For EVCT TMA, the expression of HLA-G in preeclampsia was significantly lower than that of normal pregnancy (p = 0.008), which was consistent with previously reports. This study showed that it is feasible to construct high quality of placental TMA for preeclampsia study. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Zhang, Z.; Zhang, L.; Yang, X.; Li, Y.] Zhengzhou Univ, Dept Clin Lab, Affiliated Hosp 3, Zhengzhou, Henan Province, Peoples R China. [Zhang, Z.; Yang, X.; Li, Y.] Zhengzhou Univ, Dept Obstet & Gynaecol, Affiliated Hosp 3, Zhengzhou, Henan Province, Peoples R China. [Duan, Z.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Duan, Z.] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, Z (reprint author), Dept Clin Lab, 7 KangfuQian Rd, Zhengzhou 450052, Henan Province, Peoples R China. EM zhangzhanmd@yahoo.com.cn FU Natural Science Foundation of China [30872316]; Henan science research plan [102300410005]; scientific and technical fund of the health bureau [201002011] FX This work was supported by grants from the Natural Science Foundation of China (30872316), Henan science research plan (102300410005) and the scientific and technical fund of the health bureau (201002011). NR 29 TC 4 Z9 5 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD FEB PY 2013 VL 34 IS 2 BP 187 EP 192 DI 10.1016/j.placenta.2012.11.023 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 088SJ UT WOS:000314857100016 PM 23267778 ER PT J AU Patenaude, A AF Patenaude, Andrea TI Psycho-oncology Consultation to Genetic Counselors: New Fields, New Roles SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. [Patenaude, Andrea] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 4 EP 4 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700007 ER PT J AU Meyer, F AF Meyer, Fremonta TI Tamoxifen, Mood and Antidepressants: Cases Requiring Management Decisions in the Face of Uncertain Evidence SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Meyer, Fremonta] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 19 EP 19 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700033 ER PT J AU Trevino, K Fasciano, K Prigerson, H AF Trevino, Kelly Fasciano, Karen Prigerson, Holly TI The Relationship Between the Patient-Oncologist Alliance and Treatment Adherence among Young Adults With Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Trevino, Kelly; Fasciano, Karen; Prigerson, Holly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Trevino, Kelly; Fasciano, Karen; Prigerson, Holly] Harvard Univ, Sch Med, Boston, MA USA. [Trevino, Kelly; Fasciano, Karen; Prigerson, Holly] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 23 EP 23 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700041 ER PT J AU Braun, I Rao, S Meyer, F Fedele, G AF Braun, Ilana Rao, Sowmya Meyer, Fremonta Fedele, Giuseppe TI Comparison of Psychiatric Medication Use Among Nationally Representative Long-Term Cancer Survivors and Controls SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Braun, Ilana; Meyer, Fremonta; Fedele, Giuseppe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Braun, Ilana; Meyer, Fremonta; Fedele, Giuseppe] Harvard Univ, Sch Med, Boston, MA USA. [Rao, Sowmya] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya] Vet Adm Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 32 EP 33 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700057 ER PT J AU Walling, A Dy, S Mack, J Malin, J Kim, B Pantoja, P Tisnado, D AF Walling, Anne Dy, Sydney Mack, Jennifer Malin, Jennifer Kim, Ben Pantoja, Philip Tisnado, Diana TI Evaluating the Quality of Information and Care Planning in Advanced Cancer Patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Walling, Anne; Malin, Jennifer; Tisnado, Diana] Univ Calif Los Angeles, Los Angeles, CA USA. [Dy, Sydney] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mack, Jennifer] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Malin, Jennifer; Pantoja, Philip; Tisnado, Diana] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kim, Ben] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 40 EP 40 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700069 ER PT J AU Trevino, K Gosian, J Herman, L Moye, J AF Trevino, Kelly Gosian, Jeffrey Herman, Levi Moye, Jennifer TI Spiritual Disruption and Psychological Distress in Cancer Survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Trevino, Kelly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Trevino, Kelly; Moye, Jennifer] Harvard Univ, Sch Med, Boston, MA USA. [Gosian, Jeffrey; Moye, Jennifer] Boston Healthcare Syst, Brockton, MA USA. [Herman, Levi] Michael E DeBakey VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 50 EP 50 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700085 ER PT J AU Traeger, L Eusebio, J Park, E Repper-Delisi, J Jacobo, M Convery, MS Pirl, W AF Traeger, Lara Eusebio, Justin Park, Elyse Repper-Delisi, Jennifer Jacobo, Michelle Convery, Mary Susan Pirl, William TI Psychological Skills Training for Managing Difficult Patient Encounters: Results of a Pilot Randomized Controlled Trial for Oncology Nurses SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Traeger, Lara; Eusebio, Justin; Park, Elyse; Repper-Delisi, Jennifer; Jacobo, Michelle; Convery, Mary Susan; Pirl, William] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 80 EP 81 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700139 ER PT J AU Traeger, L Jacobo, M Pirl, W AF Traeger, Lara Jacobo, Michelle Pirl, William TI Psychosocial Care of Patients With Borderline Personality Features: Balancing Change and Acceptance Oriented Approaches in Oncology Settings SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Traeger, Lara; Jacobo, Michelle; Pirl, William] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 81 EP 81 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700140 ER PT J AU Muriel, A AF Muriel, Anna TI The Value of Psychosocial Oncology: A Survey of Pediatric Oncology Providers SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Muriel, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 93 EP 94 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700162 ER PT J AU Muriel, A AF Muriel, Anna TI Developing an Integrated Service Model of Pediatric Psychosocial Oncology SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Muriel, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 94 EP 94 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700163 ER PT J AU Cooley, M Abrahm, J Braun, I Rabin, MS Fox, E Yeh, YT Halpenny, B Johns, E McCorkle, R Berry, D Finn, K Lobach, D AF Cooley, Mary Abrahm, Janet Braun, Ilana Rabin, Michael S. Fox, Erica Yeh, Yating Halpenny, Barbara Johns, Ellis McCorkle, Ruth Berry, Donna Finn, Kathleen Lobach, David TI Evaluation of a Web Service-Based Decision Support System Report Using Algorithms for Symptom Management SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Cooley, Mary; Abrahm, Janet; Braun, Ilana; Rabin, Michael S.; Fox, Erica; Yeh, Yating; Halpenny, Barbara; Berry, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johns, Ellis; Lobach, David] Duke Univ Med Ctr, Durham, NC USA. [McCorkle, Ruth] Yale Univ, New Haven, CT USA. [Finn, Kathleen] Boston Med Ctr, Boston, MA USA. [Lobach, David] Religent Hlth, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 144 EP 144 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700246 ER PT J AU Blue-Howells, JH Clark, SC van den Berk-Clark, C McGuire, JF AF Blue-Howells, Jessica H. Clark, Sean C. van den Berk-Clark, Carissa McGuire, James F. TI The US Department of Veterans Affairs Veterans Justice Programs and the Sequential Intercept Model: Case Examples in National Dissemination of Intervention for Justice-Involved Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans justice programs; criminal justice intervention; Sequential Intercept Model; community psychology; program implementation ID SUBSTANCE USE DISORDERS; SERIOUS MENTAL-ILLNESS AB Veterans are a significant subpopulation in criminal justice populations, comprising between 9% and 10% of arrestee, jail, prison, and community-supervision populations. In order to address the needs of justice-involved veterans, the U.S. Department of Veterans Affairs (VA) Veterans Justice Programs (VJP) offer services to veterans at multiple points in their involvement in the criminal justice system. Within the context of the VA's national mandate to develop VJP, this article presents best practice case examples using the Sequential Intercept Model as the intervention frame, and discusses each in context of a community psychology framework for innovation dissemination. The case examples demonstrate how central program guidance is adapted locally to meet the national mandate using strategies that fit the local environment, illustrating the innovations in action orientation, boundary spanning, and flexibility of organizations. This review provides examples of creative reinvention that expand on the mandate and work to meet local needs. To optimize services to veterans released from custody or supervised in the community, future study of the implementation of this national mandate should examine all VJP sites to identify the full range of best practices in local program implementation. C1 [Blue-Howells, Jessica H.; Clark, Sean C.; van den Berk-Clark, Carissa; McGuire, James F.] US Dept Vet Affairs, Vet Hlth Adm, Homeless Programs Off, Washington, DC USA. RP Blue-Howells, JH (reprint author), Hlth Care Reentry Vet Program, 11301 Wilshire Blvd,Mail Code W10H5, Los Angeles, CA 90073 USA. EM Jessica.Blue-Howells@va.gov OI van den Berk-Clark, Carissa/0000-0001-7712-3787 NR 21 TC 13 Z9 13 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2013 VL 10 IS 1 BP 48 EP 53 DI 10.1037/a0029652 PG 6 WC Psychology, Clinical SC Psychology GA 090TI UT WOS:000315002500005 PM 22924802 ER PT J AU Weaver, CM Joseph, D Dongon, SN Fairweather, A Ruzek, JI AF Weaver, Christopher M. Joseph, David Dongon, Shara N. Fairweather, Amy Ruzek, Josef I. TI Enhancing Services Response to Crisis Incidents Involving Veterans: A Role for Law Enforcement and Mental Health Collaboration SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans; offending; police; PTSD; crisis ID POSTTRAUMATIC-STRESS-DISORDER; POLICE OFFICERS; INTERVENTION; IRAQ; COMBAT; RISK; WAR; AGGRESSION; DIVERSION; HOSTILITY AB When crisis situations involving veterans occur, responding police officers find themselves playing an important role in the spectrum of health and mental health services for those veterans. Crisis response training can help officers respond in a manner that increases safety and optimizes outcomes for all people involved. Yet, current crisis response police training models are only accessible to select officers. Nor do they emphasize the unique challenges and strengths that impact veterans who experience acute symptoms of mental illness. In the current study, we report the results from the first generation of training, collaboratively designed to enhance officers' (a) knowledge of relevant topics, including posttraumatic stress disorder and traumatic brain injury, (b) attitudes about veterans, and (c) and skills helpful in identifying and deescalating veterans and referring them to treatment Officers completed in-class evaluations (N = 314), and a subsample (n = 53) completed 3-month follow-up evaluations. Pre- versus posttest comparisons indicated significant improvements in total score, and individually in knowledge, attitudes, and skills. Consistent with previous literature, the specific in-class gains were not retained on follow-up. However, responding officers widely endorsed use of de-escalation techniques during, and a positive impact of the training on, their interactions with veterans in the 3 months following the training. Implications for future training and policy are discussed. C1 [Weaver, Christopher M.; Dongon, Shara N.] Palo Alto Univ, Clin Psychol PhD Program, Palo Alto, CA 94143 USA. [Weaver, Christopher M.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Postraumat Stress Disorder, Palo Alto, CA USA. [Joseph, David] US Dept Vet Affairs, No Calif Hlth Care Syst, Oakland, CA USA. [Fairweather, Amy] Swords Plowshares, Coalit Iraq & Afghanistan Vet, San Francisco, CA USA. [Ruzek, Josef I.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. RP Weaver, CM (reprint author), Palo Alto Univ, Forens Psychol Program, 1791 Arastradero Rd, Palo Alto, CA 94143 USA. EM cweaver@paloaltou.edu NR 26 TC 0 Z9 0 U1 4 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2013 VL 10 IS 1 BP 66 EP 72 DI 10.1037/a0029651 PG 7 WC Psychology, Clinical SC Psychology GA 090TI UT WOS:000315002500007 PM 23088401 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Systemic Therapy for Advanced Pancreatic Neuroendocrine Tumors SO SEMINARS IN ONCOLOGY LA English DT Review ID ISLET-CELL-CARCINOMA; ENDOCRINE TUMORS; PHASE-II; LOW-GRADE; ANTITUMOR-ACTIVITY; MTOR PATHWAY; TEMOZOLOMIDE; OCTREOTIDE; EFFICACY; METHYLTRANSFERASE C1 [Kulke, Matthew H.] Dana Farber Brigham & Womens Canc Ctr, Program Neuroendocrine & Carcinoid Tumors, Boston, MA USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dana 1220, Boston, MA 02115 USA. EM Matthew_Kulke@dfci.harvard.edu FU NIH [R01 CA151532]; Dana Farber/Harvard Cancer Center SPORE in Gastrointestinal Cancer [P50 CA127003]; Saul and Gitta Kurlat fund for neuroendocrine tumor research; Robert and Ann Ramsey FX M.H. Kulke is supported in part by NIH Grant No. R01 CA151532 and the Dana Farber/Harvard Cancer Center SPORE in Gastrointestinal Cancer P50 CA127003.; The author gratefully acknowledges additional support from the Saul and Gitta Kurlat fund for neuroendocrine tumor research and from Robert and Ann Ramsey. Editorial support for the manuscript was provided by Lindy Morde. NR 67 TC 6 Z9 8 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2013 VL 40 IS 1 BP 75 EP 83 DI 10.1053/j.seminoncol.2012.11.010 PG 9 WC Oncology SC Oncology GA 089IT UT WOS:000314904900008 PM 23391115 ER PT J AU Calhoun, AW Boone, MC Miller, KH Pian-Smith, MCM AF Calhoun, Aaron W. Boone, Megan C. Miller, Karen H. Pian-Smith, May C. M. TI Case and Commentary Using Simulation to Address Hierarchy Issues During Medical Crises SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Hierarchy; Teamwork; Crisis resource management; Dysrhythmia; Hyperkalemia; Medical error; Patient simulation; Medical education; Multidisciplinary simulation; Error avoidance; Ethics; Misdirection; Simulator death; Psychological safety in simulation ID RESOURCE-MANAGEMENT; PERFORMANCE; RESIDENTS; EDUCATION; FEEDBACK; STUDENTS; STRESS; DEATH; 1ST AB Medicine is hierarchical, and both positive and negative effects of this can be exposed and magnified during a crisis. Ideally, hierarchies function in an orderly manner, but when an inappropriate directive is given, the results can be disastrous unless team members are empowered to challenge the order. This article describes a case that uses misdirection and the possibility of simulated "death" to facilitate learning among experienced clinicians about the potentially deadly effects of an unchallenged, inappropriate order. The design of this case, however, raises additional questions regarding both ethics and psychological safety. The ethical concerns that surround the use of misdirection in simulation and the psychological ramifications of incorporating patient death in this context are explored in the commentary. We conclude with a discussion of debriefing strategies that can be used to promote psychological safety during potentially emotionally charged simulations and possible directions for future research. (Sim Healthcare 8:13-19, 2013) C1 [Calhoun, Aaron W.] Univ Louisville, Sch Med, Dept Pediat, Louisville, KY 40202 USA. [Boone, Megan C.] Kosair Childrens Hosp Norton Healthcare, Just Kids Crit Care Ctr, Louisville, KY USA. [Miller, Karen H.] Univ Louisville, Coll Educ & Human Dev, Louisville, KY 40202 USA. [Miller, Karen H.] Univ Louisville, Sch Med, Louisville, KY 40202 USA. [Pian-Smith, May C. M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Pian-Smith, May C. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Calhoun, AW (reprint author), Univ Louisville, Sch Med, Dept Pediat, Div Pediat Crit Care, 571 S Floyd St,STE 332, Louisville, KY 40202 USA. EM aaron.calhoun@louisville.edu NR 35 TC 11 Z9 11 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD FEB PY 2013 VL 8 IS 1 BP 13 EP 19 DI 10.1097/SIH.0b013e318280b202 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 088AZ UT WOS:000314807500004 PM 23343842 ER PT J AU Keung, EZ Nelson, PJ Conrad, C AF Keung, Emily Z. Nelson, Peter J. Conrad, Claudius TI Concise Review: Genetically Engineered Stem Cell Therapy Targeting Angiogenesis and Tumor Stroma in Gastrointestinal Malignancy SO STEM CELLS LA English DT Review DE Mesenchymal stem cell; Genetic engineering; Gene therapy; Gastrointestinal malignancy; Angiogenesis; Stroma ID CANCER GENE-THERAPY; TRAIL-INDUCED APOPTOSIS; BONE-MARROW; PANCREATIC-CARCINOMA; BREAST-CANCER; IN-VITRO; INFARCTED MYOCARDIUM; ANTITUMOR-ACTIVITY; ENDOTHELIAL-CELLS; ADIPOSE-TISSUE AB Cell-based gene therapy holds considerable promise for the treatment of human malignancy. Genetically engineered cells if delivered to sites of disease could alleviate symptoms or even cure cancer through expression of therapeutic or suicide transgene products. Mesenchymal stem cells (MSCs), nonhematopoietic multipotent cells found primarily in bone marrow, have garnered particular interest as potential tumor-targeting vehicles due to their innate tumortropic homing properties. However, recent strategies go further than simply using MSCs as vehicles and use the stem cell-specific genetic make-up to restrict transgene expression to tumorigenic environments using tumor-tissue specific promoters. This addresses one of the concerns with this novel therapy that nonselective stem cell-based therapy could induce cancer rather than treat it. Even minimal off-target effects can be deleterious, motivating recent strategies to not only enhance MSC homing but also engineer them to make their antitumor effect selective to sites of malignancy. This review will summarize the advances made in the past decade toward developing novel cell-based cancer therapies using genetically engineered MSCs with a focus on strategies to achieve and enhance tumor specificity and their application to targeting gastrointestinal malignancies such as hepatocellular carcinoma and pancreatic adenocarcinoma. STEM CELLS 2013;31:227-235 C1 [Keung, Emily Z.; Conrad, Claudius] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nelson, Peter J.] Univ Munich, Med Klin & Poliklin 4, AG Clin Biochem, Munich, Germany. RP Conrad, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Stem Cell Inst, 55 Fruit St, Boston, MA 02114 USA. EM cconrad1@partners.org NR 82 TC 25 Z9 28 U1 1 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2013 VL 31 IS 2 BP 227 EP 235 DI 10.1002/stem.1269 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 088YE UT WOS:000314873000003 PM 23132810 ER PT J AU Fang, Y Cho, KS Tchedre, K Lee, SW Guo, CY Kinouchi, H Fried, S Sun, XH Chen, DF AF Fang, Yuan Cho, Kin-Sang Tchedre, Kissaou Lee, Seung Woo Guo, Chenying Kinouchi, Hikaru Fried, Shelley Sun, Xinghuai Chen, Dong Feng TI Ephrin-A3 Suppresses Wnt Signaling to Control Retinal Stem Cell Potency SO STEM CELLS LA English DT Article DE Adult stem cells; Cell signaling; Neural differentiation; Retina; Stem cell plasticity ID CILIARY EPITHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; GLUTAMATE TRANSPORT; ROD PHOTORECEPTORS; MARGINAL ZONE; PARS-PLANA; NEUROGENESIS; MOUSE; BODY AB The ciliary epithelium (CE) of adult mammals has been reported to provide a source of retinal stem cells (RSCs) that can give rise to all retinal cell types in vitro. A recent study, however, suggests that CE-derived cells possess properties of pigmented ciliary epithelial cells and display little neurogenic potential. Here we show that the neurogenic potential of CE-derived cells is negatively regulated by ephrin-A3, which is upregulated in the CE of postnatal mice and presents a strong prohibitory niche for adult RSCs. Addition of ephrin-A3 inhibits proliferation of CE-derived RSCs and increases pigment epithelial cell fate. In contrast, absence of ephrin-A3 promotes proliferation and increases expression of neural progenitor cell markers and photoreceptor progeny. The negative effects of ephrin-A3 on CE-derived RSCs are mediated through activation of an EphA4 receptor and suppression of Wnt3a/beta-catenin signaling. Together, our data suggest that CE-derived RSCs contain the intrinsic machinery to generate photoreceptors and other retinal neurons, while the CE of adult mice expresses negative regulators that prohibit the proliferation and neural differentiation of RSCs. Manipulating ephrin and Wnt/beta-catenin signaling may, thus, represent a viable approach in activating the endogenous neurogenic potential of CE-derived RSCs for treating photoreceptor damage and retinal degenerative disorders. STEM CELLS 2013;31:349-359 C1 [Fang, Yuan; Sun, Xinghuai] Fudan Univ, Eye & ENT Hosp, Shanghai Med Coll, Dept Ophthalmol & Visual Sci, Shanghai 200433, Peoples R China. [Fang, Yuan; Cho, Kin-Sang; Tchedre, Kissaou; Guo, Chenying; Kinouchi, Hikaru; Chen, Dong Feng] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA USA. [Lee, Seung Woo; Fried, Shelley; Chen, Dong Feng] Boston VA Healthcare Syst, Boston, MA USA. [Lee, Seung Woo; Fried, Shelley] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. RP Chen, DF (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM dongfeng.chen@schepens.harvard.edu FU NIH/NEI [R01EY017641]; NIDA [R21DA024803]; Department of Veterans Affairs [1I01RX000110]; Department of Defense [W81XWH-09-2-0091]; Lion's Foundation; National Basic Research Program of China [2007CB512204]; National Natural Science Foundation [NSFC81100667] FX The project was supported by grants from NIH/NEI (R01EY017641), NIDA (R21DA024803), Department of Veterans Affairs (1I01RX000110), Department of Defense (W81XWH-09-2-0091) to D.F.C., Lion's Foundation Grant to K.-S.C., the National Basic Research Program of China (No. 2007CB512204) to X.S., and National Natural Science Foundation (NSFC81100667) to Y.F. NR 45 TC 14 Z9 15 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2013 VL 31 IS 2 BP 349 EP 359 DI 10.1002/stem.1283 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 088YE UT WOS:000314873000014 PM 23165658 ER PT J AU Davies, TF AF Davies, Terry F. TI Is Thyroid Transplantation on the Distant Horizon? SO THYROID LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS; DIFFERENTIATION; PRESERVATION; GENERATION; ORGANOIDS; MOUSE; GLAND C1 [Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY USA. [Davies, Terry F.] James J Peters Vet Adm Med Ctr, Dept Med, New York, NY USA. RP Davies, TF (reprint author), Mt Sinai Med Ctr, Box 1055,I Gustave L Levy Pl, New York, NY 10029 USA. EM terry.davies@mssm.edu FU NIDDK NIH HHS [DK080459, DK052464, DK069713] NR 17 TC 1 Z9 1 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB PY 2013 VL 23 IS 2 BP 139 EP 141 DI 10.1089/thy.2013.2302.ed2 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088WB UT WOS:000314867300004 PM 23398160 ER PT J AU Ichinose, F AF Ichinose, Fumito TI Improving outcomes after cardiac arrest using NO inhalation SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION INJURY; AMERICAN-HEART-ASSOCIATION; EMERGENCY CARDIOVASCULAR CARE; DECREASES INFARCTION SIZE; CARDIOPULMONARY-RESUSCITATION; MYOCARDIAL-ISCHEMIA; INHALED NO; S-NITROSYLATION; MODEL AB Despite advances in cardiopulmonary resuscitation (CPR) methods including therapeutic hypothermia (TH), long-term neurological outcomes and survival after sudden cardiac arrest (CA) remains to be dismal. While nitric oxide (NO) prevents organ injury induced by ischemia and reperfusion (I/R), systemic vasodilation induced by intravenous NO-donor compounds typically precludes its use in post-CA patients in whom blood pressure is often low and unstable. Although developed as a selective pulmonary vasodilator, inhaled NO has systemic benefits in a variety of pre-clinical and clinical studies without causing potentially harmful systemic vasodilation. Breathing NO after CPR may prevent post-CA brain injury and improve long-term outcomes after CA and CPR. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Charlestown, MA 02129 USA. [Ichinose, Fumito] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 149 13th St,4315, Charlestown, MA 02129 USA. EM fichinose@partners.org FU NIH [HL101930, HL110378]; IKARIA Inc. FX This work was supported by funding from NIH R01 grants HL101930 and HL110378 and a sponsored research agreement from IKARIA Inc. NR 43 TC 5 Z9 5 U1 2 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD FEB PY 2013 VL 23 IS 2 BP 52 EP 58 DI 10.1016/j.tcm.2012.08.011 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 090YP UT WOS:000315016200005 PM 23291033 ER PT J AU Tsai, M Mori, AM Forsberg, CW Waiss, N Sporleder, JL Smith, NL Goldberg, J AF Tsai, Melyssa Mori, Alaina M. Forsberg, Christopher W. Waiss, Nicole Sporleder, Jennifer L. Smith, Nicholas L. Goldberg, Jack TI The Vietnam Era Twin Registry: A Quarter Century of Progress SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE twins; Veterans; Vietnam; aging; repository; epidemiology; genetics AB Now celebrating its 26th year of existence, the Vietnam Era Twin Registry continues to be one of the largest national samples of adult twins in the United States. The Registry twin member population is composed of 7,369 US male-male twin pair Veterans (14,738 total individuals) who served on active duty in the military during the Vietnam conflict (1964-1975). The Registry also maintains a register, data repository, and a biospecimen repository. Details on the operations of the Registry are described, as well as an overview of specific studies. Registry maintenance activities are also described, including the updating of contact information and vital status. Future plans include expanding the biospecimen repository and obtaining input from twins about study methods and diseases and conditions they would like to see investigated. C1 [Tsai, Melyssa; Mori, Alaina M.; Forsberg, Christopher W.; Waiss, Nicole; Sporleder, Jennifer L.; Smith, Nicholas L.; Goldberg, Jack] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, VET Registry, Seattle, WA USA. [Smith, Nicholas L.; Goldberg, Jack] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. RP Mori, AM (reprint author), VA Puget Sound Hlth Care Syst, VET Registry, VA MS S-152-E,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Alaina.Mori@va.gov FU Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; National Institutes of Health [DA14363, DA014363, MH60426, AA11667, AA016402, AG018386, AG022381, AA010586, AG18384, MH054636, MH055704, AA010339, AA11822, DA04604, DA009447, HL068630, HL078224, AG022982]; VA Merit Review funding; VA Cooperative Studies [256, 569]; Seattle Epidemiologic Research and Information Center; Medical College of Pennsylvania FX The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. All statements, opinions, or views are solely of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government.; The authors acknowledge the work of the following people: (1) VET Registry staff; (2) Current and past VET Registry Scientific Ethics and Oversight Committee members: J. C. Breitner, MD, MPH; E. F. Coccaro, MD; T. Colton, ScD, MS; P. Concannon, PhD; J. Harris, PhD; W. E. Nance, MD, PhD; W. True, PhD, MPH; J. S. Dorman, PhD; R. S. Paffenbarger, Jr., MD, PhD; M. M. Weissman, PhD; R. R. Williams, MD; G. Chase, PhD; and A. Bearn, MD; and (3) the many research investigators who have helped expand the VET Registry repositories. In particular, we want to acknowledge DA14363, DA014363, MH60426, AA11667, AA016402, AG018386, AG022381, AA010586, AG18384, MH054636, MH055704, AA010339, AA11822, DA04604, DA009447, HL068630, HL078224, AG022982 from the National Institutes of Health; VA Merit Review funding awarded to Drs J. Douglas Bremner, Mark Gilbertson, and Theodore Jacob; VA Cooperative Studies funding of protocols #256 and #569, and core funding for the Seattle Epidemiologic Research and Information Center; and Medical College of Pennsylvania funding awarded Dr Emil F. Coccaro. NR 9 TC 5 Z9 5 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD FEB PY 2013 VL 16 IS 1 BP 429 EP 436 DI 10.1017/thg.2012.122 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 087YD UT WOS:000314799700064 PM 23177374 ER PT J AU Graff, JN Drake, CG Beer, TM AF Graff, Julie N. Drake, Charles G. Beer, Tomasz M. TI Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research SO UROLOGY LA English DT Article ID COMBINATION THERAPY; CELL INFILTRATION; IMMUNOTHERAPY; MITOXANTRONE; PREDNISONE; DOCETAXEL; VACCINE AB OBJECTIVE To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response. MATERIALS AND METHODS We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient's response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms. RESULTS This patient's PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T. CONCLUSION Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide. UROLOGY 81: 381-383, 2013. Published by Elsevier Inc. C1 [Graff, Julie N.] Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Urol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Immunol, Baltimore, MD USA. RP Graff, JN (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,MC P3CHEMO, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Dendreon, the maker of sipuleucel-T FX T. M. Beer is a consultant to and receives funding from Dendreon, the maker of sipuleucel-T; C. G. Drake is a consultant to Dendreon. NR 14 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2013 VL 81 IS 2 BP 381 EP 383 DI 10.1016/j.urology.2012.10.044 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 086LT UT WOS:000314686000056 PM 23374810 ER PT J AU Yalla, SV AF Yalla, Subbarao V. TI Thulium Laser Enucleation Versus Plasmakinetic Resection of the Prostate: A Randomized Prospective Trial With 18-Month Follow-up EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID DYSFUNCTION C1 Harvard Univ, Sch Med, Dept Urol, VA Boston Healthcare Syst, Boston, MA 02114 USA. RP Yalla, SV (reprint author), Harvard Univ, Sch Med, Dept Urol, VA Boston Healthcare Syst, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2013 VL 81 IS 2 BP 400 EP 401 DI 10.1016/j.urology.2012.08.093 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 086LT UT WOS:000314686000062 PM 23374816 ER PT J AU O'Neil, ML Beckwith, LE Kincaid, CL Rasmussen, DD AF O'Neil, Meghan L. Beckwith, Lauren E. Kincaid, Carrie L. Rasmussen, Dennis D. TI The 1-Adrenergic Receptor Antagonist, Doxazosin, Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Noradrenergic; Doxazosin; Alcohol; Alcohol-Preferring; P Rats ID POSITIVE REINFORCING PROPERTIES; DOPAMINE-BETA-HYDROXYLASE; ALPHA-1-ADRENOCEPTOR ANTAGONIST; NORADRENERGIC MEDIATION; STARTLE RESPONSE; LABORATORY RATS; DEPENDENCE; PRAZOSIN; NEURONS; ETHANOL AB Background Evidence supports a role for the noradrenergic system in alcohol drinking in animals and humans. Our previous studies demonstrated the efficacy of prazosin, an 1-adrenergic antagonist, in decreasing alcohol drinking in rat models of alcohol dependence. Prazosin has also been shown to decrease alcohol drinking in treatment-seeking alcohol-dependent men. Clinically, the use of prazosin is limited by the requirement for multiple daily administrations, whereas doxazosin, a structurally similar 1-adrenergic antagonist, requires only once-daily dosing. In this study, we tested the hypothesis that doxazosin, like prazosin, would decrease alcohol drinking in rats selectively bred for alcohol preference (P line). Methods Adult male P rats were given 2h/d scheduled access to a 2-bottle choice (15% v/v alcohol vs. water) session 5d/wk (MF), with food and water available ad libitum 24h/d. Rats were injected with doxazosin (0 to 10mg/kg, IP) 40minutes prior to initiation of the alcohol access session in 3 trials (of 3, 5, and 5 consecutive days) each separated by 5 to 8weeks. The third trial included 1day without alcohol access (for locomotor testing), and 1day of a single hour of alcohol access (for plasma alcohol determination). Results Doxazosin significantly reduced alcohol intake in all 3 trials. The 5mg/kg dose consistently reduced alcohol intake, increased water drinking, did not affect locomotor activity, and resulted in lower plasma alcohol concentrations, suggesting that the doxazosin-induced reduction in alcohol drinking was not dependent on a motor impairment or an alteration in alcohol clearance. Conclusions Doxazosin decreases voluntary alcohol consumption by male alcohol-preferring (P) rats, supporting a role for the noradrenergic system in alcohol drinking in P rats and suggesting that doxazosin could potentially be an effective once-daily pharmacotherapeutic agent for the treatment of alcohol use disorders. C1 [O'Neil, Meghan L.; Beckwith, Lauren E.; Kincaid, Carrie L.; Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [O'Neil, Meghan L.; Beckwith, Lauren E.; Kincaid, Carrie L.; Rasmussen, Dennis D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rasmussen, Dennis D.] VISN 20 Mental Illness Res, Educ & Clin Ctr, Seattle, WA USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Med Ctr, MIRECC 116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU NIH [P20 AA017839, R24 AA015512] FX This material is based upon work supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington, and by NIH Grant P20 AA017839. P rats were provided by the Indiana Alcohol Research Resource Center, supported by NIH Grant R24 AA015512. NR 48 TC 11 Z9 11 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2013 VL 37 IS 2 BP 202 EP 212 DI 10.1111/j.1530-0277.2012.01884.x PG 11 WC Substance Abuse SC Substance Abuse GA 083ON UT WOS:000314474400005 PM 22758213 ER PT J AU Kamine, TH Barron, RJ Lesicka, A Galbraith, JD Millham, FH Larson, J AF Kamine, Tovy Haber Barron, Rebecca J. Lesicka, Agnieszka Galbraith, John D. Millham, Frederick H. Larson, Janet TI Effects of the new Accreditation Council for Graduate Medical Education work hour rules on surgical interns: a prospective study in a community teaching hospital SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Accreditation Council for Graduate Medical Education; Resident work hours; Resident exhaustion ID GENERAL-SURGERY; NIGHT-SHIFT; RESIDENTS; SLEEP; MOOD; PERFORMANCE; ATTITUDES; ALERTNESS; ROTATION; IMPACT AB BACKGROUND: On July 1, 2011, the Accreditation Council for Graduate Medical Education (ACGME) eliminated 30-hour call in an attempt to improve resident wakefulness. We surveyed interns on the Newton Wellesley Hospital (NWH) surgery service before and after the transition from Q4 overnight call to a night float schedule. METHODS: For 15 weeks, interns completed weekly surveys including the Epworth Sleepiness Scale (ESS). The service changed to a night float schedule after 3 weeks (ie, first to 3-4 and then to 6 nights in a row). RESULTS: The average ESS score rose from 9.8 +/- 5.2 to 14.9 +/- 3.1 and 14.4 +/- 4.5 (P = .042) on the 3/4 and 6/1 schedules, respectively. Interns were more likely to be abnormally tired on either night float schedule (relative risk 5 2.86; 95% confidence interval, 1.17-6.97, P = .029). CONCLUSIONS: The new ACGME work hours increased the ESS scores among interns at NWH and caused interns to be more tired than interns on the Q4 schedule. This is likely caused by the multiple nights of poor sleep without a post-call day to make up sleep. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kamine, Tovy Haber; Lesicka, Agnieszka; Millham, Frederick H.] Newton Wellesley Hosp, Dept Surg, Newton, MA 02462 USA. [Larson, Janet] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Kamine, Tovy Haber; Galbraith, John D.] BIDMC, Dept Surg, Boston, MA 02215 USA. [Barron, Rebecca J.] Brown Univ, Dept Emergency Med, Providence, RI 02903 USA. RP Kamine, TH (reprint author), Newton Wellesley Hosp, Dept Surg, 2014 Washington St, Newton, MA 02462 USA. EM tkamine@bidmc.harvard.edu NR 22 TC 10 Z9 10 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 2013 VL 205 IS 2 BP 163 EP 168 DI 10.1016/j.amjsurg.2012.10.006 PG 6 WC Surgery SC Surgery GA 086US UT WOS:000314713800009 PM 23331981 ER PT J AU LaRocque, RC Deshpande, BR Rao, SR Brunette, GW Sotir, MJ Jentes, ES Ryan, ET AF LaRocque, Regina C. Deshpande, Bhushan R. Rao, Sowmya R. Brunette, Gary W. Sotir, Mark J. Jentes, Emily S. Ryan, Edward T. CA Global TravEpiNet Consortium TI Pre-Travel Health Care of Immigrants Returning Home to Visit Friends and Relatives SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GEOSENTINEL SURVEILLANCE NETWORK; US INTERNATIONAL TRAVELERS; UNITED-STATES; ILLNESS; KNOWLEDGE; ATTITUDES; DISEASES; CLINICS; AIRPORT; RISK AB Immigrants returning home to visit friends and relatives (VFR travelers) are at higher risk of travel-associated illness than other international travelers. We evaluated 3,707 VFR and 17,507 non-VFR travelers seen for pre-travel consultation in Global TravEpiNet during 2009-2011; all were traveling to resource-poor destinations. VFR travelers more commonly visited urban destinations than non-VFR travelers (42% versus 30%, P < 0.0001); 54% of VFR travelers were female, and 18% of VFR travelers were under 6 years old. VFR travelers sought health advice closer to their departure than non-VFR travelers (median days before departure was 17 versus 26, P < 0.0001). In multivariable analysis, being a VFR traveler was an independent predictor of declining a recommended vaccine. Missed opportunities for vaccination could be addressed by improving the timing of pre-travel health care and increasing the acceptance of vaccines. Making pre-travel health care available in primary care settings may be one step to this goal. C1 [LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Deshpande, Bhushan R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Deshpande, Bhushan R.] Tufts Univ, Dept Econ, Medford, MA USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Brunette, Gary W.; Jentes, Emily S.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Sotir, Mark J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, 55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org; bdeshpande@partners.org; Sowmya.Rao@umassmed.edu; fvd3@cdc.gov; mps6@cdc.gov; ejentes@cdc.gov; etryan@partners.org FU US Centers for Disease Control and Prevention [U19CI000514, U01CK000175] FX This work was supported by US Centers for Disease Control and Prevention Grants U19CI000514 and U01CK000175. NR 22 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2013 VL 88 IS 2 BP 376 EP 380 DI 10.4269/ajtmh.2012.12-0460 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 082ZG UT WOS:000314431900029 PM 23149585 ER PT J AU Rice, IM Pohlig, RT Gallagher, JD Boninger, ML AF Rice, Ian M. Pohlig, Ryan T. Gallagher, Jerri D. Boninger, Michael. L. TI Handrim Wheelchair Propulsion Training Effect on Overground Propulsion Using Biomechanical Real-Time Visual Feedback SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Washington University Program in Occupational Therapy CY JUL 06, 2010 CL St Louis, MO DE Biomechanics; Feedback; Kinetics; Rehabilitation; Wheelchairs ID SPINAL-CORD-INJURY; CARPAL-TUNNEL SYNDROME; UPPER EXTREMITY; MECHANICAL EFFICIENCY; PUSHRIM BIOMECHANICS; PARAPLEGIC PATIENTS; EXTERNAL-FOCUS; AXLE POSITION; SHOULDER PAIN; 2 SPEEDS AB Objective: To compare the effects of 2 manual wheelchair propulsion training programs on handrim kinetics, contact angle, and stroke frequency collected during overground propulsion. Design: Randomized controlled trial comparing handrim kinetics between 3 groups: a control group that received no training, an instruction-only group that reviewed a multimedia presentation, and a feedback group that reviewed the multimedia presentation and real-time visual feedback. Setting: Research laboratory. Participants: Full-time manual wheelchair users (N=27) with spinal cord injury living in the Pittsburgh area. Interventions: Propulsion training was given 3 times over 3 weeks, and data were collected at baseline, immediately after training, and at 3 months. Main Outcome Measures: Contact angle, stroke frequency, peak resultant force, and peak rate of rise of resultant force. Results: Both feedback and instruction-only groups improved their propulsion biomechanics across all surfaces (carpet, tile, and ramp) at both target and self-selected speeds compared with the control group. While controlling for velocity, both intervention groups showed long-term reductions in the peak rate or rise of resultant force, stroke frequency, and increased contact angle. Conclusions: Long-term wheelchair users in both intervention groups significantly improved many aspects of their propulsion technique immediately after training and 3 months from baseline. Furthermore, training with a low-cost instructional video and slide presentation was an effective training tool alone. Archives of Physical Medicine and Rehabilitation 2013;94:256-63 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Rice, Ian M.] Univ Illinois, Dept Kinesiol & Community Hlth, Champaign, IL 61820 USA. [Pohlig, Ryan T.; Gallagher, Jerri D.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA. [Boninger, Michael. L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Rice, IM (reprint author), Univ Illinois, Coll Appl Hlth Sci, Dept Kinesiol & Community Hlth, Huff Hall,1206 S 4th St, Champaign, IL 61820 USA. EM ianrice@illinois.edu OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [1-R03-HD049735-01A1] NR 45 TC 10 Z9 10 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2013 VL 94 IS 2 BP 256 EP 263 DI 10.1016/j.apmr.2012.09.014 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 084TZ UT WOS:000314563300005 PM 23022092 ER PT J AU Holt, NE Percac-Lima, S Kurlinski, LA Thomas, JC Landry, PM Campbell, B Latham, N Ni, PS Jette, A Leveille, SG Bean, JF AF Holt, Nicole E. Percac-Lima, Sanja Kurlinski, Laura A. Thomas, Julia C. Landry, Paige M. Campbell, Braidie Latham, Nancy Ni, Pengsheng Jette, Alan Leveille, Suzanne G. Bean, Jonathan F. TI The Boston Rehabilitative Impairment Study of the Elderly: A Description of Methods SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Aged; Mobility limitation; Primary health care; Rehabilitation ID LOWER-EXTREMITY FUNCTION; LATE-LIFE FUNCTION; PHYSICAL PERFORMANCE BATTERY; FUNCTIONING OLDER-ADULTS; DISABILITY INSTRUMENT; LEG POWER; GERIATRIC REHABILITATION; SUBSEQUENT DISABILITY; RISK-ASSESSMENT; HEALTH ABC AB Objectives: To describe the methods of a longitudinal cohort study among older adults with preclinical disability. The study aims to address the lack of evidence guiding mobility rehabilitation for older adults by identifying those impairments and impairment combinations that are most responsible for mobility decline and disability progression over 2 years of follow-up. Design: Longitudinal cohort study. Setting: Metropolitan-based health care system. Participants: Community-dwelling primary care patients aged >= 65 years (N=430), with self-reported modification of mobility tasks because of underlying health conditions. Interventions: Not applicable. Main Outcome Measures: Late Life Function and Disability Instrument (LLFDI) (primary outcome); Short Physical Performance Battery and 400-m walk test (secondary outcomes). Results: Among 7403 primary care patients identified as being potentially eligible for participation, 430 were enrolled. Participants have a mean age of 76.5 years, are 68% women, and have on average 4.2 chronic conditions. Mean LLFDI scores are 55.5 for Function and 68.9 and 52.3 for the Disability Limitation and Frequency domains, respectively. Conclusions: Completion of our study aims will inform development of primary care based rehabilitative strategies to prevent disability. Additionally, data generated in this investigation can also serve as a vital resource for ancillary studies addressing important questions in rehabilitative science relevant to geriatric care. Archives of Physical Medicine and Rehabilitation 2013;94:347-55 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Holt, Nicole E.; Kurlinski, Laura A.; Landry, Paige M.; Campbell, Braidie; Bean, Jonathan F.] Spaulding Rehabil Hosp, Boston, MA USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, Julia C.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Latham, Nancy; Ni, Pengsheng; Jette, Alan] Boston Univ, Boston, MA 02215 USA. [Leveille, Suzanne G.] Univ Massachusetts, Boston, MA 02125 USA. RP Bean, JF (reprint author), Spaulding Cambridge Outpatient Ctr, 1575 Cambridge St, Cambridge, MA 02138 USA. EM jfbean@partners.org RI Bean, Jonathan/F-5798-2017; OI Bean, Jonathan/0000-0001-8385-8210; Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185; Holt, Nicole/0000-0002-2483-7767 FU National Institute on Aging [5 R01 AG032052-03]; National Center for Research Resources [1 UL1 RR025758-01] FX Supported by the National Institute on Aging (grant no. 5 R01 AG032052-03) and the National Center for Research Resources in a grant to the Harvard Clinical and Translational Science Center (grant no. 1 UL1 RR025758-01). NR 65 TC 14 Z9 14 U1 4 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2013 VL 94 IS 2 BP 347 EP 355 DI 10.1016/j.apmr.2012.08.217 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 084TZ UT WOS:000314563300014 PM 22989700 ER PT J AU Mitchell, T Chacko, B Ballinger, SW Bailey, SM Zhang, JH Darley-Usmar, V AF Mitchell, Tanecia Chacko, Balu Ballinger, Scott W. Bailey, Shannon M. Zhang, Jianhua Darley-Usmar, Victor TI Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE alcoholic liver disease; cellular bioenergetics; diabetes; metabolic syndrome; mitochondria; mitoquinone (MitoQ); reserve respiratory capacity; steatosis ID ALCOHOLIC LIVER-DISEASE; ANTIOXIDANT MITOQ PROTECTS; HEPATOCELLULAR-CARCINOMA; REACTIVE OXYGEN; NITRIC-OXIDE; RAT-LIVER; DEPENDENT HEPATOTOXICITY; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; RISK-FACTORS AB Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic stress, such as Type II diabetes and non-alcoholic and alcoholic steatosis, the mitochondria are subjected to multiple 'hits' such as hypoxia and oxidative and nitrative stress, which can overwhelm the mitochondrial quality control pathways. In addition, the underlying mitochondrial genetics that evolved to accommodate high-energy demand, low-calorie supply environments may now be maladapted to modern lifestyles (low-energy demand, high-calorie environments). The pro-oxidant and pro-inflammatory environment of a sedentary western lifestyle has been associated with modified redox cell signalling pathways such as steatosis, hypoxic signalling, inflammation and fibrosis. These data suggest that loss of mitochondrial quality control is intimately associated with the aberrant activation of redox cell signalling pathways under pathological conditions. In the present short review, we discuss evidence from alcoholic liver disease supporting this concept, the insights obtained from experimental models and the application of bioenergetic-based therapeutics in the context of maintaining mitochondrial quality. C1 [Mitchell, Tanecia; Chacko, Balu; Ballinger, Scott W.; Bailey, Shannon M.; Zhang, Jianhua; Darley-Usmar, Victor] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Mitchell, Tanecia; Chacko, Balu; Ballinger, Scott W.; Bailey, Shannon M.; Zhang, Jianhua; Darley-Usmar, Victor] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Darley-Usmar, V (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM darley@uab.edu FU National Institutes of Health [T32 DK007545, HL 94518, HL 103859, DK073775, AA015172, AA018841, NS064090, AA13395]; VA merit award FX This work was supported by National Institutes of Health [grant numbers T32 DK007545 (to T. M.), HL 94518 and HL 103859 (to S. B.), DK073775, AA015172 and AA018841 (to S. B.), NS064090 (to J.Z.), and AA13395 (to V.D.-U.)]. J.Z. was supported, in part, by a VA merit award. NR 61 TC 22 Z9 23 U1 2 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2013 VL 41 BP 127 EP 133 DI 10.1042/BST20120231 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080EB UT WOS:000314222900020 PM 23356271 ER PT J AU Bajwa, R McArthur, J Talano, JA Fitzgerald, J Duncan, C Margossian, S Yates, A Hall, M Cunnigham, S Spear, D Luther, K Tamburro, R AF Bajwa, Rajinder McArthur, Jennifer Talano, Julie-An Fitzgerald, Julie Duncan, Christine Margossian, Steven Yates, Andrew Hall, Mark Cunnigham, Susan Spear, Debbie Luther, Katherine Tamburro, Robert TI Assessment of Brain Natriuretic Peptide in Patients Undergoing Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Bajwa, Rajinder] Nationwide Childrens, Columbus, OH USA. [McArthur, Jennifer; Luther, Katherine] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Talano, Julie-An] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Fitzgerald, Julie] Childrens Hosp Pittsburgh, Boston, MA USA. [Duncan, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Margossian, Steven] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yates, Andrew; Hall, Mark] Nationwide Childrens Hosp, Intens Care Unit, Columbus, OH USA. [Cunnigham, Susan] Nationwide Childrens Hosp, Columbus, OH USA. [Spear, Debbie; Tamburro, Robert] Penn State Univ, Hershey Med Ctr, University Pk, PA 16802 USA. RI Bajwa, Rajinder/E-2685-2011; Yates, Andrew/E-4344-2011 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 291 BP S257 EP S258 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900289 ER PT J AU Bhatt, AS Freeman, S Herrera, A Pedamallu, CS Gevers, D Jung, J Duke, F Young, S Earl, A Kostic, A Ojesina, A Soriano, G Walker, BJ Soiffer, RJ Antin, JH Baden, L Hornick, J Marty, F Meyerson, M AF Bhatt, Ami S. Freeman, Sam Herrera, Alex Pedamallu, Chandra Sekhar Gevers, Dirk Jung, Joonil Duke, Fujiko Young, Sarah Earl, Ashlee Kostic, Aleksandar Ojesina, Akinyemi Soriano, Gabriela Walker, Bruce J. Soiffer, Robert J. Antin, Joseph H. Baden, Lindsey Hornick, Jason Marty, Francisco Meyerson, Matthew TI Sequence-Based Discovery of Novel Bacteria, Bradyrhizobium Enterica, in Cord Colitis Syndrome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Bhatt, Ami S.; Herrera, Alex; Pedamallu, Chandra Sekhar; Kostic, Aleksandar; Ojesina, Akinyemi; Soiffer, Robert J.; Antin, Joseph H.; Marty, Francisco; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Soriano, Gabriela] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Baden, Lindsey; Hornick, Jason] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 344 BP S281 EP S282 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900341 ER PT J AU Bolanos-Meade, J Logan, BR Alousi, AM Antin, JH Barowski, K Carter, SL Hexner, EO Horowitz, MM Levine, JE MacMillan, ML Martin, PJ Nakamura, R Pasquini, MC Weisdorf, DJ Westervelt, P Ho, VT AF Bolanos-Meade, Javier Logan, Brent R. Alousi, Amin M. Antin, Joseph H. Barowski, Kate Carter, Shelly L. Hexner, Elizabeth O. Horowitz, Mary M. Levine, John E. MacMillan, Margaret L. Martin, Paul J. Nakamura, Ryotaro Pasquini, Marcelo C. Weisdorf, Daniel J. Westervelt, Peter Ho, Vincent T. TI A Multi-Center, Randomized, Double Blind, Phase III Clinical Trial Comparing Steroids/Placebo Vs. Steroids/Mycophenolate Mofetil As Initial Therapy for Acute Graft-Versus-Host Disease. Blood and Marrow Transplant Clinical Trials Network Study 0802 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Bolanos-Meade, Javier] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Hexner, Elizabeth O.] Univ Penn, Philadelphia, PA 19104 USA. [Horowitz, Mary M.; Pasquini, Marcelo C.] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Levine, John E.] Univ Michigan, Ann Arbor, MI 48109 USA. [MacMillan, Margaret L.] Univ Minnesota, Pediat Blood & Marrow Transplant Program, Minneapolis, MN USA. [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Weisdorf, Daniel J.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Westervelt, Peter] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Pediat Oncol & Stem Cell Transplant, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 50 BP S137 EP S137 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900051 ER PT J AU Bredeson, C Le-Rademacher, J Zhu, XC Burkart, J Kato, K Armstrong, E Sun, YP Smith, A Ho, VT McCarthy, PL Cooke, KR Rizzo, JD Pasquini, MC AF Bredeson, Chris Le-Rademacher, Jennifer Zhu, Xiaochun Burkart, Jeanne Kato, Kazunobu Armstrong, Elizabeth Sun, Yiping Smith, Angela Ho, Vincent T. McCarthy, Philip L. Cooke, Kenneth R. Rizzo, J. Douglas Pasquini, Marcelo C. TI Improved Survival with Intravenous Busulfan (IV BU) Compared to Total Body Irradiation (TBI)-Based Myeloablative Conditioning Regimens: A CIBMTR Prospective Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Bredeson, Chris] Univ Ottawa, Ottawa, ON, Canada. [Le-Rademacher, Jennifer] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Zhu, Xiaochun; Burkart, Jeanne] CIBMTR, Milwaukee, WI USA. [Kato, Kazunobu; Armstrong, Elizabeth; Sun, Yiping; Smith, Angela] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Pediat Oncol & Stem Cell Transplant, Boston, MA 02115 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Cooke, Kenneth R.] Univ Hosp Case Western Reserve, Cleveland, OH USA. [Rizzo, J. Douglas; Pasquini, Marcelo C.] CIBMTR Med Coll Wisconsin, Dept Med, Milwaukee, WI USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 4 BP S110 EP S111 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900005 ER PT J AU Brunner, AM Chen, YB Kim, H Coughlin, E Alyea, EP Armand, P Ballen, K Cutler, C Dey, BR Glotzbecker, B Koreth, J McAfee, SL Spitzer, TR Soiffer, RJ Antin, JH Ho, VT AF Brunner, Andrew M. Chen, Yi-Bin Kim, Haesook Coughlin, Erin Alyea, Edwin P., III Armand, Philippe Ballen, Karen Cutler, Corey Dey, Bimalangshu R. Glotzbecker, Brett Koreth, John McAfee, Steven L. Spitzer, Thomas R. Soiffer, Robert J. Antin, Joseph H. Ho, Vincent T. TI Outcomes of Patients Older Than Age 70 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Brunner, Andrew M.; Chen, Yi-Bin; Coughlin, Erin; Ballen, Karen; Dey, Bimalangshu R.; McAfee, Steven L.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Haesook; Alyea, Edwin P., III; Armand, Philippe; Cutler, Corey; Koreth, John; Soiffer, Robert J.; Antin, Joseph H.; Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glotzbecker, Brett] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 10 BP S114 EP S114 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900011 ER PT J AU Chen, YB Batchelor, T Hochberg, E Brezina, M Coughlin, E Jones, S Del Rio, C Duong, A Ballen, K Barnes, J Chi, A Driscoll, J Hochberg, F LaCasce, A McAfee, SL Nayak, L Armand, P AF Chen, Yi-Bin Batchelor, Tracy Hochberg, Ephraim Brezina, Mark Coughlin, Erin Jones, SooAe Del Rio, Candice Duong, Amanda Ballen, Karen Barnes, Jeffrey Chi, Andrew Driscoll, Jessica Hochberg, Fred LaCasce, Ann McAfee, Steven L. Nayak, Lakshmi Armand, Philippe TI Phase II Trial of High-Dose Rituximab with Thiotepa/Busulfan/Cyclophosphamide (TBC) Autologous Stem Cell Transplantation for Patients with CNS Involvement by Non-Hodgkin Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Chen, Yi-Bin; Coughlin, Erin; Del Rio, Candice; Duong, Amanda; Driscoll, Jessica; McAfee, Steven L.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [LaCasce, Ann; Nayak, Lakshmi; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 37 BP S129 EP S130 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900038 ER PT J AU Chen, YB Coughlin, E Cutler, C Kennedy, K Alyea, EP Armand, P Attar, EC Ballen, K Dey, BR Koreth, J McAfee, SL Spitzer, TR Antin, JH Soiffer, RJ Ho, VT AF Chen, Yi-Bin Coughlin, Erin Cutler, Corey Kennedy, Kevin Alyea, Edwin P., III Armand, Philippe Attar, Eyal C. Ballen, Karen Dey, Bimalangshu R. Koreth, John McAfee, Steven L. Spitzer, Thomas R. Antin, Joseph H. Soiffer, Robert J. Ho, Vincent T. TI Busulfan Does Intensity and Outcomes in Reduced Intensity Allogeneic Stem Cell Transplantation for MDS/AML SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Chen, Yi-Bin; Coughlin, Erin; Attar, Eyal C.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Alyea, Edwin P., III; Armand, Philippe; Koreth, John; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen; Dey, Bimalangshu R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McAfee, Steven L.] Massachusetts Gen Hosp, Dept Med, BMT Program, Boston, MA 02114 USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Pediat Oncol & Stem Cell Transplant, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 11 BP S114 EP S115 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900012 ER PT J AU Cuccovia, BA Lehmann, L Margossian, S Buia-Amport, S Rosati, C AF Cuccovia, Barbara Ann Lehmann, Leslie Margossian, Steven Buia-Amport, Stephanie Rosati, Christine TI What Tools are in Your Toolbox to Promote Change? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Cuccovia, Barbara Ann; Buia-Amport, Stephanie] Boston Childrens Hosp, Boston, MA USA. [Lehmann, Leslie; Rosati, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Margossian, Steven] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 485 BP S351 EP S351 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900482 ER PT J AU Duran-Struuck, R Climov, M Gusha, A Harrington, E Matar, AJ Crepeau, RL Spitzer, TR Sachs, DH Huang, CA AF Duran-Struuck, Raimon Climov, Mihail Gusha, Ashley Harrington, Edward Matar, Abraham J. Crepeau, Rebecca L. Spitzer, Thomas R. Sachs, David H. Huang, Christene A. TI Immune Modulation of Antibody Responses Induced Through Allogeneic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Duran-Struuck, Raimon; Climov, Mihail; Gusha, Ashley; Harrington, Edward; Matar, Abraham J.; Crepeau, Rebecca L.; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Duran-Struuck, Raimon; Climov, Mihail; Sachs, David H.; Huang, Christene A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Matar, Abraham J.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplantat Unit, Boston, MA 02114 USA. [Spitzer, Thomas R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 354 BP S286 EP S287 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900351 ER PT J AU Duran-Struuck, R Murphy, GE Bronson, RT Sachs, DH Huang, CA Spitzer, TR AF Duran-Struuck, Raimon Murphy, George E. Bronson, Roderick T. Sachs, David H. Huang, Christene A. Spitzer, Thomas R. TI The MGH Miniature Swine as a Large Animal Model of HCT and Graft Versus Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Duran-Struuck, Raimon; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Duran-Struuck, Raimon; Sachs, David H.; Huang, Christene A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Murphy, George E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplantat Unit, Boston, MA 02114 USA. [Spitzer, Thomas R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 355 BP S287 EP S287 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900352 ER PT J AU Fackler, LS Tilearcio, MC Yoon, C Phillips, KS AF Fackler, Lauren S. Tilearcio, Marion C. Yoon, Clara Phillips, Kimberly S. TI A Comprehensive Review of DFCI's Adult HSCT Data SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Fackler, Lauren S.; Tilearcio, Marion C.; Yoon, Clara; Phillips, Kimberly S.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 326 BP S274 EP S274 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900324 ER PT J AU King, B Geary, J Crown, D Sturtevant, O Anderson, S Stasko, K Emmert, A Luckey, CJ AF King, Bethany Geary, Joshua Crown, Donna Sturtevant, Olive Anderson, Sharon Stasko, Karl Emmert, Amy Luckey, C. John TI Implementing Novel Predictive Parameters in Apheresis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [King, Bethany; Sturtevant, Olive; Luckey, C. John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geary, Joshua; Anderson, Sharon; Stasko, Karl] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. [Crown, Donna; Luckey, C. John] Brigham & Womens Hosp, Kraft Family Blood Donor Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 490 BP S353 EP S354 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900487 ER PT J AU Krajewski, J Radhakrishnan, K Chen, N Ricci, A Geyer, M Harrison, L Ozkaynak, MF Satwani, P Cheerva, A Talano, JA Moore, TB Gillio, AP Baxter-Lowe, LA Cairo, MS AF Krajewski, Jennifer Radhakrishnan, Kavita Chen, Nan Ricci, Angela Geyer, Mark Harrison, Lauren Ozkaynak, M. Fevzi Satwani, Prakash Cheerva, Alexandra Talano, Julie-An Moore, Theodore B. Gillio, Alfred P. Baxter-Lowe, Lee Ann Cairo, Mitchell S. TI Low Day 100 Transplant-Related Mortality (TRM) and Relapse Rate Following Clofarabine in Combination With Cytarabine, Total Body Irradiation and Allogeneic Stem Cell Transplantation in Children, Adolescents and Young Adults with Poor-Risk Acute Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Krajewski, Jennifer] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Radhakrishnan, Kavita; Chen, Nan; Ricci, Angela; Harrison, Lauren; Ozkaynak, M. Fevzi; Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Geyer, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Satwani, Prakash] Columbia Univ, New York, NY USA. [Cheerva, Alexandra] Univ Louisville, Louisville, KY 40292 USA. [Talano, Julie-An] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Moore, Theodore B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gillio, Alfred P.] HUMC, Hackensack, NJ USA. [Baxter-Lowe, Lee Ann] UCSF, Immunogent & Transplantat Lab, San Francsico, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 278 BP S251 EP S251 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900276 ER PT J AU Li, LQ Nellore, A McDonough, SM Politikos, I Kim, H Nikiforow, S Soiffer, RJ Antin, JH Ballen, K Cutler, C Ritz, J Boussiotis, VA AF Li, Lequn Nellore, Anoma McDonough, Sean M. Politikos, Ioannis Kim, Haesook Nikiforow, Sarah Soiffer, Robert J. Antin, Joseph H. Ballen, Karen Cutler, Corey Ritz, Jerome Boussiotis, Vassiliki A. TI Ex Vivo Treatment of Umbilical Cord Blood with Prostaglandin E2 Alters the Molecular and Functional Properties of T Cells Via Modulating Wnt/beta-Catenin Signaling SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Li, Lequn; Nellore, Anoma; Politikos, Ioannis; Boussiotis, Vassiliki A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Sch Med, Boston, MA 02215 USA. [McDonough, Sean M.; Kim, Haesook; Nikiforow, Sarah; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 70 BP S148 EP S148 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900071 ER PT J AU Lill, M Costa, LJ Yeh, RF Lim, S Stuart, R Waller, EK Shore, T Craig, M Freytes, CO Shea, TC Rodriguez, TE Flinn, IW Comeau, T Yeager, AM Pulsipher, MA Bence-Bruckler, I Laneuville, P Bierman, PJ Chen, AI Yu, LH Patil, S Sun, YP Armstrong, E Smith, A Elekes, A Kato, K Vaughan, W AF Lill, Michael Costa, Luciano J. Yeh, Rosa F. Lim, Stephen Stuart, Robert Waller, Edmund K. Shore, Tsiporah Craig, Michael Freytes, Cesar O. Shea, Thomas C. Rodriguez, Tulio E. Flinn, Ian W. Comeau, Terrance Yeager, Andrew M. Pulsipher, Michael A. Bence-Bruckler, Isabelle Laneuville, Pierre Bierman, Philip J. Chen, Andy I. Yu, Louie H. Patil, Shiva Sun, Yiping Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Vaughan, William TI Pharmacokinetic-Directed Dose Adjustment Is Essential for Intravenous Busulfan Exposure Optimization: Findings From a Multi-Center Phase II Study of Autologous Hematopoietic Stem Cell Transplantation for Lymphoma in North America SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Lill, Michael; Lim, Stephen] Cedars Sinai Med Ctr, Blood & Marrow Transplant Program, Los Angeles, CA 90048 USA. [Costa, Luciano J.; Stuart, Robert] Med Univ S Carolina, Charleston, SC 29425 USA. [Yeh, Rosa F.; Yu, Louie H.] Seattle Canc Care Alliance, Seattle, WA USA. [Waller, Edmund K.] Emory Univ, Bone Marrow & Stem Cell Transplant Program, Atlanta, GA 30322 USA. [Shore, Tsiporah] Cornell Univ, Weill Med Coll, Bone Marrow & Stem Cell Transplantat Program, New York, NY 10021 USA. [Shore, Tsiporah] New York Presbyterian Hosp, New York, NY USA. [Craig, Michael] W Virginia Univ, Osborn Heme Malignancy & Transplant Serv, Morgantown, WV 26506 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, Hematopoiet Stem Cell Transplant Program, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Shea, Thomas C.] Univ N Carolina, Dept Med, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Rodriguez, Tulio E.] Loyola Univ, Chicago Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Flinn, Ian W.] Sarah Cannon Sarah Cannon Res Inst, Nashville, TN USA. [Comeau, Terrance] New Brunswick Stem Cell Transplant Program, St John, NB, Canada. [Yeager, Andrew M.] Blood & Marrow Transplantat Program, Tucson, AZ USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Div Hematol & Hematol Malignancies,Primary Childr, Salt Lake City, UT USA. [Bence-Bruckler, Isabelle] Univ Ottawa, Ottawa Hosp, Ottawa, ON, Canada. [Laneuville, Pierre] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Bierman, Philip J.] Univ Nebraska Med Ctr, Dept Internal Med, BMT, Omaha, NE USA. [Chen, Andy I.] Oregon Hlth & Sci, Hematol Malignancies, Portland, OR USA. [Patil, Shiva; Sun, Yiping; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceutical Dev & Commercializat Inc, Princeton, NJ USA. [Vaughan, William] Univ Alabama Birmingham, Bone Marrow Transplantat Program, Birmingham, AL USA. NR 0 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 41 BP S132 EP S132 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900042 ER PT J AU Murase, K Kawano, Y Ryan, J Matsuoka, KI Bascug, G McDonough, SM Smith, R Lazo-Kallanian, S Daley, J Koreth, J Soiffer, RJ Letai, A Ritz, J AF Murase, Kazuyuki Kawano, Yutaka Ryan, Jeremy Matsuoka, Ken-ichi Bascug, Gregory McDonough, Sean M. Smith, Robert Lazo-Kallanian, Suzan Daley, John Koreth, John Soiffer, Robert J. Letai, Anthony Ritz, Jerome TI Regulation of Apoptotic Pathways in Human Regulatory T Cells in Chronic Graft Versus Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Murase, Kazuyuki; Kawano, Yutaka; Ryan, Jeremy; Matsuoka, Ken-ichi; Bascug, Gregory; McDonough, Sean M.; Smith, Robert; Lazo-Kallanian, Suzan; Daley, John; Koreth, John; Soiffer, Robert J.; Letai, Anthony; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 56 BP S140 EP S141 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900057 ER PT J AU Nikiforow, S McDonough, SM Emerson, RO Hamm, D Kim, H Ballen, K Boussiotis, VA Soiffer, RJ Antin, JH Ritz, J Cutler, C AF Nikiforow, Sarah McDonough, Sean M. Emerson, Ryan O. Hamm, David Kim, Haesook Ballen, Karen Boussiotis, Vassiliki A. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome Cutler, Corey TI Evolution of T Cell Repertoire Diversity After Reduced-Intensity Conditioning and Double Umbilical Cord Blood Transplantation with or without Exposure to FT1050 (16,16-dimethyl Prostaglandin E2) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Nikiforow, Sarah; McDonough, Sean M.; Kim, Haesook; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boussiotis, Vassiliki A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 187 BP S206 EP S207 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900185 ER PT J AU Nikiforow, S Kim, H Kao, G Sainvil, MM McDonough, SM Armand, P Ho, VT Alyea, EP Cutler, C Ritz, J Antin, JH Soiffer, RJ Koreth, J AF Nikiforow, Sarah Kim, Haesook Kao, Grace Sainvil, Marie-Michele McDonough, Sean M. Armand, Philippe Ho, Vincent T. Alyea, Edwin P., III Cutler, Corey Ritz, Jerome Antin, Joseph H. Soiffer, Robert J. Koreth, John TI CD25+ Regulatory T CELL-Depleted Donor Lymphocyte Infusion for Relapse After Allogeneic Transplantation - A PHASE 1 Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Nikiforow, Sarah; Kao, Grace; Armand, Philippe; Ho, Vincent T.; Alyea, Edwin P., III; Cutler, Corey; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Koreth, John] Harvard Univ, Sch Med, Boston, MA USA. [Nikiforow, Sarah; Kim, Haesook; Kao, Grace; Sainvil, Marie-Michele; McDonough, Sean M.; Armand, Philippe; Ho, Vincent T.; Alyea, Edwin P., III; Cutler, Corey; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Koreth, John] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 48 BP S135 EP S136 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900049 ER PT J AU Palmer, J Chai, XY Martin, PJ Kurland, BF Pavletic, SZ Inamoto, Y Arora, M Cutler, C Weisdorf, DJ Flowers, MED Jagasia, MH Arai, S Pidala, J Lee, SJ AF Palmer, Jeanne Chai, Xiaoyu Martin, Paul J. Kurland, Brenda F. Pavletic, Steven Z. Inamoto, Yoshihiro Arora, Mukta Cutler, Corey Weisdorf, Daniel J. Flowers, Mary E. D. Jagasia, Madan H. Arai, Sally Pidala, Joseph Lee, Stephanie J. TI Pulmonary Symptoms Measured by the NIH Lung Score Predict Overall Survival and Non-Relapse Mortality in Chronic GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Chai, Xiaoyu; Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Martin, Paul J.; Kurland, Brenda F.; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 456 BP S336 EP S337 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900453 ER PT J AU Pidala, J Chai, XY Martin, PJ Inamoto, Y Flowers, MED Cutler, C Palmer, J Weisdorf, DJ Pavletic, SZ Arora, M Arai, S Lee, SJ AF Pidala, Joseph Chai, Xiaoyu Martin, Paul J. Inamoto, Yoshihiro Flowers, Mary E. D. Cutler, Corey Palmer, Jeanne Weisdorf, Daniel J. Pavletic, Steven Z. Arora, Mukta Arai, Sally Lee, Stephanie J. TI Utility of Grip Strength and 2 Minute Walk Test in Chronic GVHD Assessment: An Analysis From the Chronic GVHD Consortium SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chai, Xiaoyu; Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Martin, Paul J.; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 458 BP S338 EP S338 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900455 ER PT J AU Politikos, I Kim, H Brown, J McDonough, SM Li, LQ Cutler, C Soiffer, RJ Antin, JH Ballen, K Ritz, J Boussiotis, VA AF Politikos, Ioannis Kim, Haesook Brown, Julia McDonough, Sean M. Li, Lequn Cutler, Corey Soiffer, Robert J. Antin, Joseph H. Ballen, Karen Ritz, Jerome Boussiotis, Vassiliki A. TI Markers of Angiogenesis and Neovascularization Correlate with Functional Recovery of Thymic Epithelial Cells and T Cell Immune Reconstitution After Cord Blood Transplantation in Adults SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Politikos, Ioannis; Brown, Julia; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Kim, Haesook; McDonough, Sean M.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Politikos, Ioannis/0000-0002-8925-2399 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 72 BP S149 EP S149 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900073 ER PT J AU Radhakrishnan, K Geyer, M Morris, E Baxter-Lowe, LA Cairo, MS AF Radhakrishnan, Kavita Geyer, Mark Morris, Erin Baxter-Lowe, Lee Ann Cairo, Mitchell S. TI Reduced Toxicity Conditioning with Busulfan, Fludarabine, Alemtuzumab and Allogeneic Stem Cell Transplantation From HLA-Matched Sibling Donors in Children with High Risk Sickle Cell Disease Results in Long Term Donor Chimerism and Low Incidence of aGVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Radhakrishnan, Kavita] Yale Univ, Sch Med, New Haven, CT USA. [Geyer, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Morris, Erin; Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Baxter-Lowe, Lee Ann] UCSF, Immunogent & Transplantat Lab, San Francsico, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 100 BP S164 EP S165 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900101 ER PT J AU Raley, DY Glotzbecker, B Deangelo, D Stone, R Soiffer, RJ Alyea, EP AF Raley, Deborah Yolin Glotzbecker, Brett Deangelo, Daniel Stone, Richard Soiffer, Robert J. Alyea, Edwin P., III TI A Retrospective Review Comparing Outcomes of Patients Receiving Reinduction Therapy on House Staff and PA Services SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Raley, Deborah Yolin; Deangelo, Daniel; Stone, Richard; Alyea, Edwin P., III] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glotzbecker, Brett] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 240 BP S232 EP S232 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900238 ER PT J AU Ratanatharathorn, V Stadtmauer, EA Yeh, RF Freytes, CO Toro, JJ Akpek, G Sahovic, E Tricot, GJ Shaughnessy, PJ White, DJ Rodriguez, TE Solomon, SR Yu, LH Patil, S Sun, YP Armstrong, E Smith, A Elekes, A Kato, K Reece, DE AF Ratanatharathorn, Voravit Stadtmauer, Edward A. Yeh, Rosa F. Freytes, Cesar O. Toro, Juan J. Akpek, Gorgun Sahovic, Entezam Tricot, Guido J. Shaughnessy, Paul J. White, Darrell J. Rodriguez, Tulio E. Solomon, Scott R. Yu, Louie H. Patil, Shiva Sun, Yiping Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Reece, Donna E. TI Safety and Efficacy From Intravenous Busulfan with PLC-Directed Dosed Adjustment and Bortezomib Conditioning Regimen in Relapsed Multiple Myeloma Patients Undergoing a Second Autologous Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Ratanatharathorn, Voravit] Karmanos Canc Inst, Detroit, MI USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Yeh, Rosa F.; Yu, Louie H.] Seattle Canc Care Alliance, Seattle, WA USA. [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Akpek, Gorgun] Univ Maryland, Med Ctr, Med Greenebaum Canc Ctr BMT, Baltimore, MD 21201 USA. [Sahovic, Entezam] Western Pennsylvania Canc Inst, Pittsburgh, PA USA. [Tricot, Guido J.] Univ Utah, Sch Med, Div Hematol, BMT & Myeloma Program, Salt Lake City, UT USA. [Shaughnessy, Paul J.] Texas Transplant Inst, San Antonio, TX USA. [White, Darrell J.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Med, Div Hematol, Halifax, NS, Canada. [White, Darrell J.] Dalhousie Univ, Halifax, NS B3H 3J5, Canada. [Rodriguez, Tulio E.] Loyola Univ Chicago, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Solomon, Scott R.] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Patil, Shiva; Sun, Yiping; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 146 BP S186 EP S187 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900146 ER PT J AU Rosenblatt, J Avivi, I Vasir, D Uhl, L Katz, T Somaiya, P Mills, H Joyce, R Levine, JD Boussiotis, VA Luptakova, K Arnason, J Drummy, N Delaney, C Breault, E Held, V Bisharat, L Giallombardo, N Mortellite, J Wagoner, J Schickler, M Rotem-Yehudar, R Richardson, PG Laubach, J Anderson, K Munshi, N Rowe, J Kufe, D Avigan, D AF Rosenblatt, Jacalyn Avivi, Irit Vasir, David Uhl, Lynne Katz, Tami Somaiya, Poorvi Mills, Heidi Joyce, Robin Levine, James D. Boussiotis, Vassiliki A. Luptakova, Katarina Arnason, Jon Drummy, Natalie Delaney, Carol Breault, Emma Held, Viki Bisharat, Lina Giallombardo, Nancy Mortellite, Jamie Wagoner, Judith Schickler, Michael Rotem-Yehudar, Rinat Richardson, Paul G. Laubach, Jacob Anderson, Kenneth Munshi, Nikhil Rowe, Jacob Kufe, Donald Avigan, David TI Blockade of PD-1 in Combination with Dendritic Cell/Myeloma Fusion Cell Vaccination Following Autologous Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Rosenblatt, Jacalyn; Uhl, Lynne; Somaiya, Poorvi; Mills, Heidi; Joyce, Robin; Levine, James D.; Boussiotis, Vassiliki A.; Luptakova, Katarina; Drummy, Natalie; Delaney, Carol; Breault, Emma; Giallombardo, Nancy; Mortellite, Jamie; Wagoner, Judith; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Avivi, Irit; Katz, Tami; Held, Viki; Bisharat, Lina; Rowe, Jacob] Rambam Med Ctr, Haifa, Israel. [Vasir, David; Richardson, Paul G.; Laubach, Jacob; Anderson, Kenneth; Munshi, Nikhil; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 1 BP S109 EP S109 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900002 ER PT J AU Stadtmauer, EA Sullivan, K Marty, F Dadwa, SS Papanicoleau, GA Shea, TC Mossad, SB Andreadis, C Young, JA Buadi, F Schuster, MG Idrissi, M Heineman, T Berkowitz, EM AF Stadtmauer, Edward A. Sullivan, Keith Marty, Francisco Dadwa, Sanjeet S. Papanicoleau, Genovefa A. Shea, Thomas C. Mossad, Sherif B. Andreadis, Charalambos Young, Jo-Anne Buadi, Francis Schuster, Mindy G. Idrissi, Mohamed Heineman, Thomas Berkowitz, Elchonon M. TI One-Year Safety and Immunogenicity of Two Formulations of an Adjuvanted Varicella-Zoster Virus (VZV) Subunit Candidate Vaccine in Adult Autologous Hematopoietic Cell Transplant (HCT) Recipients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Stadtmauer, Edward A.; Schuster, Mindy G.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Sullivan, Keith] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Marty, Francisco] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dadwa, Sanjeet S.] City Hope Natl Med Ctr, Duarte, CA USA. [Papanicoleau, Genovefa A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shea, Thomas C.] Univ N Carolina, Dept Med, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Mossad, Sherif B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Andreadis, Charalambos] UCSF, BMT, San Francisco, CA USA. [Young, Jo-Anne] Univ Minnesota, Minneapolis, MN USA. [Buadi, Francis] UT Blood & Marrow Transplant Ctr, Memphis, TN USA. [Idrissi, Mohamed] GlaxoSmithKline Vaccines, Wavre, Belgium. [Heineman, Thomas; Berkowitz, Elchonon M.] GlaxoSmithKline Vaccines, King Of Prussia, PA USA. RI Young, Jo-Anne/G-2617-2013 OI Young, Jo-Anne/0000-0003-4182-341X NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 107 BP S168 EP S169 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900108 ER PT J AU Toro, JJ Schneider, D Lee, S Smith, GM Gushiken, F Haile, DJ Freytes, CO AF Toro, Juan J. Schneider, Deanna Lee, Shuko Smith, Gregory M. Gushiken, Francisco Haile, David J. Freytes, Cesar O. TI Is Edentulism Associated with Lower Bacteremia and Transplant-Associated Toxicities in Patients with Multiple Myeloma? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Toro, Juan J.; Schneider, Deanna; Lee, Shuko; Smith, Gregory M.; Gushiken, Francisco; Haile, David J.; Freytes, Cesar O.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 322 BP S272 EP S272 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900320 ER PT J AU Vander Lugt, M Braun, T Hanash, S Ferrara, JLM Ritz, J Ho, VT Antin, JH Zhang, Q Chin, A Gomez, A Harris, AC Levine, JE Choi, SW Couriel, DR Reddy, P Paczesny, S AF Vander Lugt, Mark Braun, Thomas Hanash, Samir Ferrara, James L. M. Ritz, Jerome Ho, Vincent T. Antin, Joseph H. Zhang, Qing Chin, Alice Gomez, Aurelie Harris, Andrew C. Levine, John E. Choi, Sung Won Couriel, Daniel R. Reddy, Pavan Paczesny, Sophie TI Plasma ST2 Concentrations Predict Acute Gvhd Development and Non-Relapse Mortality SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Vander Lugt, Mark; Ferrara, James L. M.; Gomez, Aurelie; Harris, Andrew C.; Levine, John E.; Choi, Sung Won; Reddy, Pavan] Univ Michigan, Ann Arbor, MI 48109 USA. [Braun, Thomas; Couriel, Daniel R.; Paczesny, Sophie] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Hanash, Samir; Zhang, Qing; Chin, Alice] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ritz, Jerome; Ho, Vincent T.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 60 BP S142 EP S143 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900061 ER PT J AU Wood, WA Chai, XY Weisdorf, DJ Martin, PJ Cutler, C Inamoto, Y Wolff, D Pavletic, SZ Pidala, J Palmer, J Arora, M Arai, S Jagasia, MH Storer, B Lee, SJ Mitchell, S AF Wood, William A. Chai, Xiaoyu Weisdorf, Daniel J. Martin, Paul J. Cutler, Corey Inamoto, Yoshihiro Wolff, Daniel Pavletic, Steven Z. Pidala, Joseph Palmer, Jeanne Arora, Mukta Arai, Sally Jagasia, Madan H. Storer, Barry Lee, Stephanie J. Mitchell, Sandra TI Association of Comorbidity Scoring with Outcome in Patients with Chronic Graft Versus Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Wood, William A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Chapel Hill, NC 27599 USA. [Chai, Xiaoyu; Inamoto, Yoshihiro; Storer, Barry] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wolff, Daniel] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Mitchell, Sandra] NIH, Res & Practice Dev Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 463 BP S340 EP S341 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900460 ER PT J AU Yanik, G Ho, VT Horowitz, M Weisdorf, DJ Logan, BR Wu, J Soiffer, RJ Wingard, JR Levine, JE Ferrara, JLM Giralt, SA White, E Carter, SL DiFronzo, N Cooke, KR AF Yanik, Gregory Ho, Vincent T. Horowitz, Mary Weisdorf, Daniel J. Logan, Brent R. Wu, Juan Soiffer, Robert J. Wingard, John R. Levine, John E. Ferrara, James L. M. Giralt, Sergio A. White, Eric Carter, Shelly L. DiFronzo, Nancy Cooke, Kenneth R. TI Randomized, Double Blind, Placebo-Controlled Trial of a TNF Inhibitor (ETANERCEPT) for the Treatment of Idiopathic Pneumonia Syndrome (IPS) After Allogeneic Stem Cell Transplant (SCT). A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Yanik, Gregory] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Pediat Oncol & Stem Cell Transplant, Boston, MA 02115 USA. [Horowitz, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Wu, Juan; Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wingard, John R.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA. [Levine, John E.; Ferrara, James L. M.; White, Eric] Univ Michigan, Ann Arbor, MI 48109 USA. [Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, New York, NY 10021 USA. [DiFronzo, Nancy] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Cooke, Kenneth R.] Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 108 BP S169 EP S169 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900109 ER PT J AU Yeh, AC Brunner, AM Spitzer, TR Chen, YB Coughlin, E McAfee, SL Ballen, K Attar, EC Caron, ML Preffer, F Yeap, B Dey, BR AF Yeh, Albert C. Brunner, Andrew M. Spitzer, Thomas R. Chen, Yi-Bin Coughlin, Erin McAfee, Steven L. Ballen, Karen Attar, Eyal C. Caron, Martin L. Preffer, Frederick Yeap, Beow Dey, Bimalangshu R. TI Lower Uric Acid Level At the Time of Allogeneic Hematopoietic Cell Transplantation (HCT) Is Protective Against Acute Graft-Vs-Host-Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Yeh, Albert C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Brunner, Andrew M.; Coughlin, Erin; Ballen, Karen; Preffer, Frederick; Dey, Bimalangshu R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplantat Unit, Boston, MA 02114 USA. [Chen, Yi-Bin; Attar, Eyal C.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [McAfee, Steven L.] Massachusetts Gen Hosp, Dept Med, BMT Program, Boston, MA 02114 USA. [Caron, Martin L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Yeap, Beow] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 62 BP S143 EP S144 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900063 ER PT J AU Yolin, D Glotzbecker, B Soiffer, RJ Antin, J Alyea, EP AF Yolin, Deborah Glotzbecker, Brett Soiffer, Robert J. Antin, Joseph Alyea, Edwin P., III TI Reducing Inappropriate Testing Following NCCN and IDSA Guidelines in Autologous Stem Cell Transplant (SCT) Patients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Yolin, Deborah; Glotzbecker, Brett; Soiffer, Robert J.; Alyea, Edwin P., III] Dana Farber Canc Inst, Boston, MA 02115 USA. [Antin, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 159 BP S193 EP S193 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900159 ER PT J AU Hendricks, AM Amara, J Baker, E Charns, MP Gardner, JA Iverson, KM Kimerling, R Krengel, M Meterko, M Pogoda, TK Stolzmann, KL Lew, HL AF Hendricks, Ann M. Amara, Jomana Baker, Errol Charns, Martin P. Gardner, John A. Iverson, Katherine M. Kimerling, Rachel Krengel, Maxine Meterko, Mark Pogoda, Terri K. Stolzmann, Kelly L. Lew, Henry L. TI Screening for mild traumatic brain injury in OEF-OIF deployed US military: An empirical assessment of VHA's experience SO BRAIN INJURY LA English DT Article DE Afghanistan; blast injuries; brain injuries; depression; Iraq; non-blast injuries; post-traumatic stress disorder; screening; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; POLYTRAUMA CLINICAL TRIAD; MENTAL-HEALTH PROBLEMS; VETERANS; IRAQ; AFGHANISTAN; CARE; TBI; CHALLENGES AB Background: VHA screens for traumatic brain injury (TBI) among patients formerly deployed to Afghanistan or Iraq, referring those who screen positive for a Comprehensive TBI Evaluation (CTBIE). Methods: To assess the programme, rates were calculated of positive screens for potential TBI in the population of patients screened in VHA between October 2007 through March 2009. Rates were derived of TBI confirmed by comprehensive evaluations from October 2008 through July 2009. Patient characteristics were obtained from Department of Defense and VHA administrative data. Results: In the study population, 21.6% screened positive for potential TBI and 54.6% of these had electronic records of a CTBIE. Of those with CTBIE records, evaluators confirmed TBI in 57.7%, yielding a best estimate that 6.8% of all those screened were confirmed to have TBI. Three quarters of all screened patients and virtually all those evaluated (whether TBI was confirmed or not) had VHA care the following year. Conclusions: VHA's TBI screening process is inclusive and has utility in referring patients with current symptoms to appropriate care. More than 90% of those evaluated received further VHA care and confirmatory evaluations were associated with significantly higher average utilization. Generalizability is limited to those who seek VHA healthcare. C1 [Hendricks, Ann M.; Baker, Errol; Charns, Martin P.; Gardner, John A.; Iverson, Katherine M.; Krengel, Maxine; Meterko, Mark; Pogoda, Terri K.; Stolzmann, Kelly L.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Hendricks, Ann M.; Charns, Martin P.; Meterko, Mark; Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Amara, Jomana] USN, Postgrad Sch, DRMI, Monterey, CA USA. [Iverson, Katherine M.; Krengel, Maxine] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Lew, Henry L.] Def & Vet Brain Injury Ctr, Richmond, VA USA. [Lew, Henry L.] Univ Hawaii Manoa, Honolulu, HI 96822 USA. RP Hendricks, AM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,152 H, Boston, MA 02130 USA. EM ahendricksphd@gmail.com OI Charns, Martin/0000-0002-7102-5331; Krengel, Maxine/0000-0001-7632-590X; Kimerling, Rachel/0000-0003-0996-4212 FU Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs [SDR 08-405] FX This paper is based on work supported by the Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs, through SDR 08-405. The opinions expressed in this article are the authors' and do not reflect those of the Department of Veterans Affairs, the Veterans Health Administration, Health Services Research and Development, the Defense and Veterans Brain Injury Center or the Department of Defense. We thank Douglas Bidelspach, David Cifu, Carlos Tun and three anonymous reviewers for comments on prior versions of this paper. NR 41 TC 14 Z9 14 U1 1 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD FEB PY 2013 VL 27 IS 2 BP 125 EP 134 DI 10.3109/02699052.2012.729284 PG 10 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 083PX UT WOS:000314478500001 PM 23384211 ER PT J AU Drezner, JA Ackerman, MJ Anderson, J Ashley, E Asplund, CA Baggish, AL Borjesson, M Cannon, BC Corrado, D DiFiori, JP Fischbach, P Froelicher, V Harmon, KG Heidbuchel, H Marek, J Owens, DS Paul, S Pelliccia, A Prutkin, JM Salerno, JC Schmied, CM Sharma, S Stein, R Vetter, VL Wilson, MG AF Drezner, Jonathan A. Ackerman, Michael John Anderson, Jeffrey Ashley, Euan Asplund, Chad A. Baggish, Aaron L. Borjesson, Mats Cannon, Bryan C. Corrado, Domenico DiFiori, John P. Fischbach, Peter Froelicher, Victor Harmon, Kimberly G. Heidbuchel, Hein Marek, Joseph Owens, David S. Paul, Stephen Pelliccia, Antonio Prutkin, Jordan M. Salerno, Jack C. Schmied, Christian M. Sharma, Sanjay Stein, Ricardo Vetter, Victoria L. Wilson, Mathew G. TI Electrocardiographic interpretation in athletes: the 'Seattle Criteria' SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID ECG INTERPRETATION; ACCURACY AB Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athlete's ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13-14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD. C1 [Drezner, Jonathan A.; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Ackerman, Michael John] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Dept Pediat, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Div Pediat Cardiol, Rochester, MN USA. [Anderson, Jeffrey] Univ Connecticut, Dept Athlet, Storrs, CT USA. [Ashley, Euan; Froelicher, Victor] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA. [Asplund, Chad A.] Eisenhower Army Med Ctr, Dept Family Med, Ft Gordon, GA USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Borjesson, Mats] Karolinska Univ Hosp, Swedish Sch Sports & Hlth Sci, Dept Cardiol, Stockholm, Sweden. [Cannon, Bryan C.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Corrado, Domenico] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [DiFiori, John P.] Univ Calif Los Angeles, Dept Family Med, Div Sports Med, Los Angeles, CA USA. [Fischbach, Peter] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Heidbuchel, Hein] Univ Louvain, Dept Cardiovasc Sci, Louvain, Belgium. [Marek, Joseph] Midwest Heart Fdn, Oak Brook Terrace, IL USA. [Owens, David S.; Prutkin, Jordan M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Paul, Stephen] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. [Pelliccia, Antonio] Inst Sport Med & Sci, Dept Med, Rome, Italy. [Salerno, Jack C.] Seattle Childrens Hosp, Div Cardiol, Seattle, WA USA. [Schmied, Christian M.] Univ Zurich Hosp, Ctr Cardiovasc, Div Cardiol, CH-8091 Zurich, Switzerland. [Sharma, Sanjay] St Georges Univ London, Dept Cardivasc Sci, London, England. [Stein, Ricardo] Hosp Clin Porto Alegre, Dept Cardiol, Porto Alegre, RS, Brazil. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. [Wilson, Mathew G.] Qatar Orthoped & Sports Med Hosp, ASPETAR, Dept Sports Med, Doha, Qatar. RP Drezner, JA (reprint author), Univ Washington, Dept Family Med, 1959 NE Pacific St,Box 356390, Seattle, WA 98195 USA. EM jdrezner@uw.edu OI Borjesson, Mats/0000-0002-8786-0438; Owens, David/0000-0002-7293-9688 NR 11 TC 166 Z9 169 U1 4 U2 34 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD FEB PY 2013 VL 47 IS 3 BP 122 EP 124 DI 10.1136/bjsports-2012-092067 PG 3 WC Sport Sciences SC Sport Sciences GA 081VE UT WOS:000314349700002 PM 23303758 ER PT J AU Drezner, JA Fischbach, P Froelicher, V Marek, J Pelliccia, A Prutkin, JM Schmied, CM Sharma, S Wilson, MG Ackerman, MJ Anderson, J Ashley, E Asplund, CA Baggish, AL Borjesson, M Cannon, BC Corrado, D DiFiori, JP Harmon, KG Heidbuchel, H Owens, DS Paul, S Salerno, JC Stein, R Vetter, VL AF Drezner, Jonathan A. Fischbach, Peter Froelicher, Victor Marek, Joseph Pelliccia, Antonio Prutkin, Jordan M. Schmied, Christian M. Sharma, Sanjay Wilson, Mathew G. Ackerman, Michael John Anderson, Jeffrey Ashley, Euan Asplund, Chad A. Baggish, Aaron L. Borjesson, Mats Cannon, Bryan C. Corrado, Domenico DiFiori, John P. Harmon, Kimberly G. Heidbuchel, Hein Owens, David S. Paul, Stephen Salerno, Jack C. Stein, Ricardo Vetter, Victoria L. TI Normal electrocardiographic findings: recognising physiological adaptations in athletes SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID EARLY REPOLARIZATION PATTERN; HYPERTROPHIC CARDIOMYOPATHY; CLINICAL-SIGNIFICANCE; ECG; PREVALENCE; HEART; CRITERIA; POPULATION; CARDIOLOGY; CONDUCTION AB Electrocardiographic changes in athletes are common and usually reflect benign structural and electrical remodelling of the heart as a physiological adaptation to regular and sustained physical training (athlete's heart). The ability to identify an abnormality on the 12-lead ECG, suggestive of underlying cardiac disease associated with sudden cardiac death (SCD), is based on a sound working knowledge of the normal ECG characteristics within the athletic population. This document will assist physicians in identifying normal ECG patterns commonly found in athletes. The ECG findings presented as normal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine. C1 [Drezner, Jonathan A.; Fischbach, Peter; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Fischbach, Peter] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Froelicher, Victor; Ashley, Euan] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA. [Marek, Joseph] Midwest Heart Fdn, Oak Brook Terrace, IL USA. [Pelliccia, Antonio] Inst Sport Med & Sci, Dept Med, Rome, Italy. [Prutkin, Jordan M.; Owens, David S.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Schmied, Christian M.] Univ Zurich Hosp, Div Cardiol, CH-8091 Zurich, Switzerland. [Sharma, Sanjay] St Georges Univ London, Dept Cardivasc Sci, London, England. [Wilson, Mathew G.] Qatar Orthoped & Sports Med Hosp, ASPETAR, Dept Sports Med, Doha, Qatar. [Ackerman, Michael John] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Dept Med, Dept Pediat Cardiol, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Dept Pediat, Rochester, MN USA. [Ackerman, Michael John] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Anderson, Jeffrey] Univ Connecticut, Dept Athlet, Storrs, CT USA. [Asplund, Chad A.] Eisenhower Army Med Ctr, Dept Family Med, Ft Gordon, GA USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Borjesson, Mats] Karolinska Univ Hosp, Swedish Sch Sports & Hlth Sci, Dept Cardiol, Stockholm, Sweden. [Cannon, Bryan C.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Corrado, Domenico] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [DiFiori, John P.] Univ Calif Los Angeles, Div Sports Med, Los Angeles, CA USA. [Heidbuchel, Hein] Univ Louvain, Dept Cardiovasc Sci, Louvain, Belgium. [Paul, Stephen] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. [Salerno, Jack C.] Seattle Childrens Hosp, Div Cardiol, Seattle, WA USA. [Stein, Ricardo] Hosp Clin Porto Alegre, Dept Cardiol, Porto Alegre, RS, Brazil. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. RP Drezner, JA (reprint author), Univ Washington, Dept Family Med, 1959 NE Pacific St,Box 356390, Seattle, WA 98195 USA. EM jdrezner@uw.edu OI Borjesson, Mats/0000-0002-8786-0438; Owens, David/0000-0002-7293-9688 NR 35 TC 48 Z9 50 U1 0 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD FEB PY 2013 VL 47 IS 3 BP 125 EP + DI 10.1136/bjsports-2012-092068 PG 13 WC Sport Sciences SC Sport Sciences GA 081VE UT WOS:000314349700003 PM 23303759 ER PT J AU Drezner, JA Ashley, E Baggish, AL Borjesson, M Corrado, D Owens, DS Patel, A Pelliccia, A Vetter, VL Ackerman, MJ Anderson, J Asplund, CA Cannon, BC DiFiori, J Fischbach, P Froelicher, V Harmon, KG Heidbuchel, H Marek, J Paul, S Prutkin, JM Salerno, JC Schmied, CM Sharma, S Stein, R Wilson, M AF Drezner, Jonathan A. Ashley, Euan Baggish, Aaron L. Borjesson, Mats Corrado, Domenico Owens, David S. Patel, Akash Pelliccia, Antonio Vetter, Victoria L. Ackerman, Michael J. Anderson, Jeff Asplund, Chad A. Cannon, Bryan C. DiFiori, John Fischbach, Peter Froelicher, Victor Harmon, Kimberly G. Heidbuchel, Hein Marek, Joseph Paul, Stephen Prutkin, Jordan M. Salerno, Jack C. Schmied, Christian M. Sharma, Sanjay Stein, Ricardo Wilson, Mathew TI Abnormal electrocardiographic findings in athletes: recognising changes suggestive of cardiomyopathy SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID LEFT-VENTRICULAR NONCOMPACTION; PRIMARY PULMONARY-HYPERTENSION; BUNDLE-BRANCH BLOCK; DISTINGUISHING HYPERTROPHIC CARDIOMYOPATHY; CARDIOVASCULAR MAGNETIC-RESONANCE; FAMILIAL DILATED CARDIOMYOPATHY; ST-SEGMENT ELEVATION; SUDDEN-DEATH; NON-COMPACTION; SYSTOLIC DYSFUNCTION AB Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine. C1 [Drezner, Jonathan A.; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Ashley, Euan; Froelicher, Victor] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Borjesson, Mats] Karolinska Univ Hosp, Swedish Sch Sports & Hlth Sci, Dept Cardiol, Stockholm, Sweden. [Corrado, Domenico] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [Owens, David S.; Prutkin, Jordan M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Patel, Akash; Vetter, Victoria L.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. [Pelliccia, Antonio] Inst Sport Med & Sci, Dept Med, Rome, Italy. [Ackerman, Michael J.] Mayo Clin, Dept Med, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Dept Pediat, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Ackerman, Michael J.; Cannon, Bryan C.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Div Pediat Cardiol, Rochester, MN USA. [Anderson, Jeff] Univ Connecticut, Dept Athlet, Storrs, CT USA. [Asplund, Chad A.] Eisenhower Army Med Ctr, Dept Family Med, Ft Gordon, GA USA. [DiFiori, John] Univ Calif Los Angeles, Div Sports Med, Los Angeles, CA USA. [Fischbach, Peter] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Heidbuchel, Hein] Univ Louvain, Dept Cardiovasc Sci, Louvain, Belgium. [Marek, Joseph] Midwest Heart Fdn, Oak Brook Terrace, IL USA. [Paul, Stephen] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. [Salerno, Jack C.] Seattle Childrens Hosp, Div Cardiol, Seattle, WA USA. [Schmied, Christian M.] Univ Zurich Hosp, Div Cardiol, CH-8091 Zurich, Switzerland. [Sharma, Sanjay] St Georges Univ London, Dept Cardiovasc Sci, London, England. [Stein, Ricardo] Hosp Clin Porto Alegre, Dept Cardiol, Porto Alegre, RS, Brazil. [Wilson, Mathew] Qatar Orthoped & Sports Med Hosp, ASPETAR, Dept Sports Med, Doha, Qatar. RP Drezner, JA (reprint author), Univ Washington, Dept Family Med, 1959 NE Pacific St,Box 356390, Seattle, WA 98195 USA. EM jdrezner@uw.edu OI Borjesson, Mats/0000-0002-8786-0438; Owens, David/0000-0002-7293-9688 NR 91 TC 46 Z9 46 U1 0 U2 22 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD FEB PY 2013 VL 47 IS 3 BP 137 EP + DI 10.1136/bjsports-2012-092069 PG 18 WC Sport Sciences SC Sport Sciences GA 081VE UT WOS:000314349700004 PM 23303760 ER PT J AU Drezner, JA Ackerman, MJ Cannon, BC Corrado, D Heidbuchel, H Prutkin, JM Salerno, JC Anderson, J Ashley, E Asplund, CA Baggish, AL Borjesson, M DiFiori, JP Fischbach, P Froelicher, V Harmon, KG Marek, J Owens, DS Paul, S Pelliccia, A Schmied, CM Sharma, S Stein, R Vetter, VL Wilson, MG AF Drezner, Jonathan A. Ackerman, Michael J. Cannon, Bryan C. Corrado, Domenico Heidbuchel, Hein Prutkin, Jordan M. Salerno, Jack C. Anderson, Jeffrey Ashley, Euan Asplund, Chad A. Baggish, Aaron L. Borjesson, Mats DiFiori, John P. Fischbach, Peter Froelicher, Victor Harmon, Kimberly G. Marek, Joseph Owens, David S. Paul, Stephen Pelliccia, Antonio Schmied, Christian M. Sharma, Sanjay Stein, Ricardo Vetter, Victoria L. Wilson, Mathew G. TI Abnormal electrocardiographic findings in athletes: recognising changes suggestive of primary electrical disease SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID LONG-QT-SYNDROME; PARKINSON-WHITE-SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA; SUDDEN UNEXPLAINED DEATH; HEART-RHYTHM-SOCIETY; PROPOSED DIAGNOSTIC-CRITERIA; EXPERT CONSENSUS STATEMENT; OF-CARDIOLOGY FOUNDATION; BRUGADA-SYNDROME; CARDIAC DEATH AB Cardiac channelopathies are potentially lethal inherited arrhythmia syndromes and an important cause of sudden cardiac death (SCD) in young athletes. Other cardiac rhythm and conduction disturbances also may indicate the presence of an underlying cardiac disorder. The 12-lead ECG is utilised as both a screening and a diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of a pathological cardiac disease. This article describes ECG findings present in primary electrical diseases afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine. C1 [Drezner, Jonathan A.; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Ackerman, Michael J.] Mayo Clin, Dept Med, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Dept Pediat, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Ackerman, Michael J.; Cannon, Bryan C.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Ackerman, Michael J.] Mayo Clin, Div Pediat Cardiol, Rochester, MN USA. [Corrado, Domenico] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [Heidbuchel, Hein] Univ Louvain, Dept Cardiovasc Sci, Louvain, Belgium. [Prutkin, Jordan M.; Owens, David S.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Salerno, Jack C.] Seattle Childrens Hosp, Div Cardiol, Seattle, WA USA. [Anderson, Jeffrey] Univ Connecticut, Dept Athlet, Storrs, CT USA. [Ashley, Euan; Froelicher, Victor] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA. [Asplund, Chad A.] Eisenhower Army Med Ctr, Dept Family Med, Ft Gordon, GA USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Borjesson, Mats] Karolinska Univ Hosp, Swedish Sch Sports & Hlth Sci, Stockholm, Sweden. [Borjesson, Mats] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden. [DiFiori, John P.] Univ Calif Los Angeles, Div Sports Med, Los Angeles, CA USA. [Fischbach, Peter] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Marek, Joseph] Midwest Heart Fdn, Oak Brook Terrace, IL USA. [Paul, Stephen] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. [Pelliccia, Antonio] Inst Sport Med & Sci, Dept Med, Rome, Italy. [Schmied, Christian M.] Univ Zurich Hosp, Div Cardiol, CH-8091 Zurich, Switzerland. [Sharma, Sanjay] St Georges Univ London, Dept Cardiovasc Sci, London, England. [Stein, Ricardo] Hosp Clin Porto Alegre, Dept Cardiol, Porto Alegre, RS, Brazil. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. [Wilson, Mathew G.] Qatar Orthoped & Sports Med Hosp, ASPETAR, Dept Sports Med, Doha, Qatar. RP Drezner, JA (reprint author), Univ Washington, Dept Family Med, 1959 NE Pacific St,Box 356930, Seattle, WA 98195 USA. EM jdrezner@uw.edu OI Borjesson, Mats/0000-0002-8786-0438; Owens, David/0000-0002-7293-9688 NR 67 TC 42 Z9 43 U1 0 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD FEB PY 2013 VL 47 IS 3 BP 153 EP + DI 10.1136/bjsports-2012-092070 PG 17 WC Sport Sciences SC Sport Sciences GA 081VE UT WOS:000314349700005 PM 23303761 ER PT J AU Dhar, DK Damink, SWMO Brindley, JH Godfrey, A Chapman, MH Sandanayake, NS Andreola, F Mazurek, S Hasan, T Malago, M Pereira, SP AF Dhar, Dipok Kumar Damink, Steven W. M. Olde Brindley, James Hal Godfrey, Andrew Chapman, Michael H. Sandanayake, Neomal S. Andreola, Fausto Mazurek, Sybille Hasan, Tayyaba Malago, Massimo Pereira, Stephen P. TI Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer SO CANCER LA English DT Article DE pyruvate kinase M2; cholangiocarcinoma; invasion; angiogenesis; diagnosis ID INTRAHEPATIC CHOLANGIOCARCINOMA; HEPATOCELLULAR-CARCINOMA; PLASMA; CELLS; SERUM; IDENTIFICATION; METABOLISM; EXPRESSION; DISEASES; TUM2-PK AB BACKGROUND: The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC. METHODS: Plasma and bile M2-PK concentrations were measured by enzyme-linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing techniques. RESULTS: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas silencing in an M2-PKpositive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PKtransfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation. CONCLUSIONS: Bile M2-PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNAmediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target. Cancer 2013. (C) 2012 American Cancer Society. C1 [Dhar, Dipok Kumar; Brindley, James Hal; Godfrey, Andrew; Chapman, Michael H.; Sandanayake, Neomal S.; Andreola, Fausto; Pereira, Stephen P.] UCL, Sch Med, UCL Inst Liver & Digest Hlth, London NW3 2PF, England. [Dhar, Dipok Kumar; Damink, Steven W. M. Olde; Malago, Massimo] UCL, Sch Med, Acad Dept Surg, London NW3 2PF, England. [Damink, Steven W. M. Olde] Maastricht Univ, Dept Surg, Med Ctr, Maastricht, Netherlands. [Damink, Steven W. M. Olde] Maastricht Univ, Nutr & Toxicol Res Inst NUTRIM, Maastricht, Netherlands. [Mazurek, Sybille] Univ Giessen, Inst Vet Physiol & Biochem, D-35390 Giessen, Germany. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pereira, SP (reprint author), UCL, Sch Med, UCL Inst Liver & Digest Hlth, Royal Free Campus, London NW3 2PF, England. EM stephen.pereira@ucl.ac.uk FU US National Institutes of Health [PO1CA84203]; UK Medical Research Council [G0801588]; Charitable Research Fund East and North Herts National Health Service Trust; Jason Boas Charitable Fund; UK Department of Health's National Institute for Health Research Biomedical Research Centres FX This study was supported in part by US National Institutes of Health grant PO1CA84203, UK Medical Research Council grant (G0801588), and Charitable Research Fund East and North Herts National Health Service Trust. Dipok Kumar Dhar is a Jason Boas Research Fellow, and this work was partly funded by the Jason Boas Charitable Fund. The work was undertaken at UCL Hospital/UCL, which receives a proportion of funding from the UK Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. NR 27 TC 11 Z9 11 U1 1 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2013 VL 119 IS 3 BP 575 EP 585 DI 10.1002/cncr.27611 PG 11 WC Oncology SC Oncology GA 075IN UT WOS:000313878500018 PM 22864959 ER PT J AU Lennes, IT Temel, JS Hoedt, C Meilleur, A Lamont, EB AF Lennes, Inga T. Temel, Jennifer S. Hoedt, Christen Meilleur, Ashley Lamont, Elizabeth B. TI Predictors of newly diagnosed cancer patients' understanding of the goals of their care at initiation of chemotherapy SO CANCER LA English DT Article DE elderly; chemotherapy; treatment understanding; limited English speakers; chemotherapy ID OF-LIFE CONVERSATIONS; EARLY PALLIATIVE CARE; CELL LUNG-CANCER; HEALTH LITERACY; COLORECTAL-CANCER; PROGNOSTIC DISCLOSURE; TREATMENT PREFERENCES; PATIENTS PERCEPTIONS; COMMUNICATION; END AB BACKGROUND: The American Society of Clinical Oncology Quality Oncology Practice Initiative endorses in their core measures that providers should discuss the goals of care (GOC) at the time of chemotherapy consent. GOC refers to chemotherapy treatment intent: cure versus noncure. In this study, the authors sought to determine whether attributes of patients and initial patient-physician encounters were associated with patients' understanding of their GOC. METHODS: In total, the authors surveyed 125 consecutive, newly diagnosed patients who were receiving chemotherapy for solid malignancies at a single academic cancer center and performed a medical record review for additional data. Patient understanding of their oncologist's GOC and oncologist's reported GOC were compared. The primary outcome was concordance of patient-physician dyads regarding the GOC (cure vs noncure). RESULTS: One hundred twenty-five of 137 of eligible patients (91%) completed the survey. Only 95 of 125 patient-physician pairs (75%) patient-physician pairs were concordant regarding the GOC. In a multivariable logistic regression, both older patients (odds ratio, 0.21; 95% confidence interval, 0.08-0.57) and non-native English speakers had an almost 80% lower odds (odds ratio, 0.23; 95% confidence interval, 0.05-0.93) of GOC concordance compared with younger patients and native English speakers. Patients who received printed chemotherapy information during the patient-physician consent process had almost 3 times greater odds (odds ratio, 2.88; 95% confidence interval, 1.24-6.68) of GOC concordance with their physician compared with those who did not receive materials. CONCLUSIONS: Patient misunderstanding of GOC was substantial, with 25% of cancer patients misunderstanding the goal of their chemotherapy treatment. Key predictors of GOC misunderstanding included factors that potentially were amenable to interventions at the time of chemotherapy consent. Cancer 2013. (C) 2012 American Cancer Society. C1 [Lennes, Inga T.; Temel, Jennifer S.; Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lennes, Inga T.; Temel, Jennifer S.; Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meilleur, Ashley; Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Hoedt, Christen] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. RP Lennes, IT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Profess Off Bldg,55 Fruit St, Boston, MA 02114 USA. EM ilennes@partners.org FU Cancer Center Program in Cancer Outcomes Research Training (PCORT) Fellowship (National Institutes of Health) [R25CA092203] FX This study was supported by a Cancer Center Program in Cancer Outcomes Research Training (PCORT) Fellowship (National Institutes of Health grant R25CA092203). NR 38 TC 6 Z9 6 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2013 VL 119 IS 3 BP 691 EP 699 DI 10.1002/cncr.27787 PG 9 WC Oncology SC Oncology GA 075IN UT WOS:000313878500031 PM 23011902 ER PT J AU Naito, M Hainz, U Burkhardt, UE Fu, BY Ahove, D Stevenson, KE Rajasagi, M Zhu, BG Alonso, A Witten, E Matsuoka, KI Neuberg, D Duke-Cohan, JS Wu, CJ Freeman, GJ AF Naito, Masayasu Hainz, Ursula Burkhardt, Ute E. Fu, Buyin Ahove, Deborah Stevenson, Kristen E. Rajasagi, Mohini Zhu, Baogong Alonso, Anselmo Witten, Elizabeth Matsuoka, Ken-ichi Neuberg, Donna Duke-Cohan, Jonathan S. Wu, Catherine J. Freeman, Gordon J. TI CD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CD40; CD40L; B lymphocytes; Immunotherapy; Antigen-presenting cell ID HIGH-LEVEL EXPRESSION; T-CELLS; MAMMALIAN-CELLS; GITR LIGAND; IN-VITRO; PROTEINS; IMMUNITY; IMMUNOTHERAPY; VECTORS; ANTIBODIES AB CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker. C1 [Naito, Masayasu; Hainz, Ursula; Burkhardt, Ute E.; Ahove, Deborah; Rajasagi, Mohini; Alonso, Anselmo; Witten, Elizabeth; Duke-Cohan, Jonathan S.; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Naito, Masayasu; Hainz, Ursula; Burkhardt, Ute E.; Fu, Buyin; Ahove, Deborah; Rajasagi, Mohini; Zhu, Baogong; Alonso, Anselmo; Witten, Elizabeth; Matsuoka, Ken-ichi; Duke-Cohan, Jonathan S.; Wu, Catherine J.; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, Kristen E.; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Duke-Cohan, Jonathan S.; Wu, Catherine J.; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. EM cwu@partners.org; gordon_freeman@dfci.harvard.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU Early Career Physician-Scientist Award of the Howard Hughes Medical Institute; Blavatnik Family Foundation; Innovative Research Grant of SU2C/AACR; Leukemia and Lymphoma Translational Research Program; Damon-Runyon Clinical Investigator award [CI-3807]; NIH [P01 AI056299, R01-AI089955, P01-AI1054456, 5HSSN266200500030C]; [R01-ITL102532]; [R01-CA155010] FX We would like especially to thank Drs. Richard Kornbluth, Teru Hideshima, Tetsuro Sasada, Yutaka Kawano, and Jerome Ritz for their insightful suggestions. CJW acknowledges support from R01-ITL102532, R01-CA155010, the Early Career Physician-Scientist Award of the Howard Hughes Medical Institute, the Blavatnik Family Foundation, an Innovative Research Grant of SU2C/AACR, the Leukemia and Lymphoma Translational Research Program, and a Damon-Runyon Clinical Investigator award (CI-3807). GF is supported by NIH grants P01 AI056299, R01-AI089955, P01-AI1054456, and 5HSSN266200500030C. NR 27 TC 8 Z9 9 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2013 VL 62 IS 2 BP 347 EP 357 DI 10.1007/s00262-012-1331-4 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 087NN UT WOS:000314768500013 PM 22926059 ER PT J AU Mascaux, C Feser, WJ Lewis, MT Baron, AE Coldren, CD Merrick, DT Kennedy, TC Eckelberger, JI Rozeboom, LM Franklin, WA Minna, JD Bunn, PA Miller, YE Keith, RL Hirsch, FR AF Mascaux, Celine Feser, William J. Lewis, Marina T. Baron, Anna E. Coldren, Christopher D. Merrick, Daniel T. Kennedy, Timothy C. Eckelberger, John I. Rozeboom, Leslie M. Franklin, Wilbur A. Minna, John D. Bunn, Paul A. Miller, York E. Keith, Robert L. Hirsch, Fred R. TI Endobronchial miRNAs as Biomarkers in Lung Cancer Chemoprevention SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MICRORNA EXPRESSION; DNA HYPERMETHYLATION; COLORECTAL-CANCER; GENE-EXPRESSION; CIGARETTE-SMOKE; CARCINOGENESIS; ADENOCARCINOMA; METHYLATION; METASTASIS AB Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analog) with placebo in high-risk subjects showed improvement in bronchial histology in former, but not current, smokers. This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoint and predictive biomarkers to incorporate into chemoprevention trials. Matched bronchial biopsies were obtained at baseline and at 6-month follow-up from 125 high-risk individuals who completed the trial: 31/29 and 37/28 current/former smokers in the iloprost and placebo arm, respectively. We analyzed the expression of 14 selected miRNAs by Real Time PCR in 496 biopsies. The expression of seven miRNAs was significantly correlated with histology at baseline. The expression of miR-34c was inversely correlated with histology at baseline (P < 0.0001) and with change in histology at follow-up (P = 0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was upregulated at baseline (P < 0.0001) and downregulated after treatment with iloprost (P = 0.0023). No miRNA at baseline reliably predicted a response to iloprost. No biomarker predictive of response to iloprost was found. MiR-34c was inversely correlated with baseline histology and with histology changes. Mir-34c changes at follow-up could be used as a quantitative biomarker that parallels histologic response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies. Cancer Prev Res; 6(2); 100-8. (C)2012 AACR. C1 [Mascaux, Celine; Eckelberger, John I.; Rozeboom, Leslie M.; Bunn, Paul A.; Hirsch, Fred R.] Colorado Sch Publ Hlth, Dept Med, Div Med Oncol, Aurora, CO USA. [Feser, William J.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Lewis, Marina T.; Baron, Anna E.; Merrick, Daniel T.; Franklin, Wilbur A.; Hirsch, Fred R.] Colorado Sch Publ Hlth, Dept Pathol, Aurora, CO USA. [Coldren, Christopher D.; Kennedy, Timothy C.; Miller, York E.; Keith, Robert L.] Colorado Sch Publ Hlth, Div Pulm Sci & Crit Care Med, Aurora, CO USA. Univ Colorado, Sch Med, Aurora, CO USA. [Merrick, Daniel T.; Miller, York E.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Coldren, Christopher D.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Minna, John D.] Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, Dallas, TX USA. [Minna, John D.] Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Pharmacol, Dallas, TX USA. RP Mascaux, C (reprint author), Univ Colorado Denver, Div Med Oncol, 12801 E 17th Ave,Mail Stop 8177, Aurora, CO 80045 USA. EM celinejmmascaux@gmail.com FU Specialized Program of Research Excellence (SPORE) Career Development Award; Lung Cancer Biomarkers and Chemoprevention Consortium (LCBCC); International Association for the Study of Lung Cancer (IASLC); Louisiana Chapter of the National Lung Cancer Partnership (NLCP); Gary L. and Thelissa Zollinger Early Detection of Lung Cancer Endowment Fund; Colorado SPORE in Lung Cancer [NCI P50 CA58187, NCI RO1 CA164780]; Texas SPORE in Lung Cancer [P50 CA070907]; Department of Veterans Affairs Merit Review Program FX This work was financially supported by a Specialized Program of Research Excellence (SPORE) Career Development Award (C. Mascaux) and by Lung Cancer Biomarkers and Chemoprevention Consortium (LCBCC) funds (C. Mascaux and F.R. Hirsch). C. Mascaux was also supported by a fellowship from the International Association for the Study of Lung Cancer (IASLC), a grant from the Louisiana Chapter of the National Lung Cancer Partnership (NLCP), and a grant from the Gary L. and Thelissa Zollinger Early Detection of Lung Cancer Endowment Fund. Additional support was provided from the Colorado SPORE in Lung Cancer NCI P50 CA58187, NCI RO1 CA164780, Texas SPORE in Lung Cancer (P50 CA070907), Department of Veterans Affairs Merit Review Program (to R.L. Keith). NR 36 TC 4 Z9 4 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2013 VL 6 IS 2 BP 100 EP 108 DI 10.1158/1940-6207.CAPR-12-0382 PG 9 WC Oncology SC Oncology GA 086IF UT WOS:000314676600005 PM 23268837 ER EF